Hippocampal Integrity Research Articles

Inhalation of H2/O2 (66.7 %/33.3 %) mitigates depression-like behaviors in diabetes mellitus complicated with depression mice via suppressing inflammation and preventing hippocampal damage

Diabetes mellitus complicated with depression (DD) is a prevalent psychosomatic disorder. It is characterized by severe cognitive impairment, and associated with high rates of disability and mortality. Although conventional treatment options are available, the efficacy of these regimens in managing DD remains limited. Molecular hydrogen (H2), a selective hydroxyl radical scavenger, has shown therapeutic potential in the treatment of various systemic diseases. This study aims to investigate the therapeutic effects of H2 on DD. A DD mouse model was established through intraperitoneal injection of streptozotocin (STZ, 150 mg/kg) and lipopolysaccharide (LPS, 0.5 mg/kg). Following the induction of DD, the mice were treated with H2/O2 (66.7 %/33.3 %)inhalation for 7 days. Behavioral assessments were conducted by standard behavioral tests, and the levels of inflammatory cytokines in peripheral blood serum and hippocampal tissue were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, magnetic resonance imaging (MRI) scans and immunofluorescence staining of the hippocampus were performed to evaluate hippocampal structural integrity. The results demonstrated that inhalation of H2/O2 (66.7 %/33.3 %) significantly ameliorated depressive behaviors and symptoms in DD mice, reversed hippocampal volume reduction, decreased inflammatory cytokine levels in peripheral blood serum and hippocampal tissue, and inhibited the activation of A1 astrocytes in the hippocampus. Our study suggests that H2/O2 (66.7 %/33.3 %) inhalation therapy may offer a promising treatment strategy for DD and its associated symptoms.

Effects of Vitamin C on Aluminum Chloride- Induced Neurotoxicity on the Hippocampal Cortex of Adult Wistar Male Rats

This study aimed to evaluate the neuroprotective effects of Vitamin C on aluminum chloride (AlCl₃)- induced brain damage, focusing on behavioral, biochemical, and histomorphological outcomes in a rodent model. Study Design: A total of 42 healthy male rats were randomly assigned to three groups: control, AlCl₃ -only, and AlCl₃ plus Vitamin C (500 mg/kg and 1000 mg/kg). The AlCl₃ groups received daily doses of AlCl₃, while the Vitamin C groups received concurrent Vitamin C supplementation. Methodology: Body weight, behavioral changes, biochemical markers of oxidative stress (MDA, SOD, GSH), and inflammation (TNF-α, IL-6) were assessed. Histomorphological analysis of the hippocampus was performed to evaluate structural damage. Behavioral assessments included locomotor and exploratory activity tests. Biochemical analyses measured oxidative stress and antioxidant enzyme activities. Results: AlCl₃ administration resulted in significant body weight loss, increased oxidative stress (elevated MDA, and SOD levels), and heightened inflammation (elevated TNF-α and IL-6). Behavioral tests showed increased excitatory activities, and increased anxiety levels as seen in increased rearing and grooming activities. Histomorphological examination revealed significant hippocampal damages as seen in the pale staining, shrunken pyramidal cells. Vitamin C co- administration mitigated these adverse effects, demonstrating reduced body weight loss, lower oxidative stress, decreased inflammation, and improved behavioral performance. Histological analysis indicated less hippocampal damage in the Vitamin C treated groups. Conclusion: As an antioxidant, Vitamin C effectively attenuates the neurotoxic effects of AlCl₃ by reducing oxidative stress and inflammation, and by protecting the hippocampal cellular integrity. These findings suggest that Vitamin C holds potential as a therapeutic agent for mitigating neurotoxicity induced by aluminum compounds.

Exercise, memory, and the hippocampus: Uncovering modifiable lifestyle reserve factors in refractory epilepsy

Physical exercise is an emerging target for improving cognition in aging and neurological disease. Due to the beneficial impact of exercise on hippocampal health and the vulnerability of the hippocampus in medication-resistant temporal lobe epilepsy (TLE), exercise could present a promising intervention in TLE. We investigated whether exercise engagement is associated with verbal memory function and hippocampal integrity in 29 young to middle-aged adults with refractory TLE and 21 demographically matched controls. Participants completed a self-reported questionnaire of weekly exercise, three tests of verbal memory, and a subset (n = 44) underwent structural MRI. Individuals with TLE self-reported lower exercise scores than controls across all levels of exercise intensity (p < 0.001). In TLE, greater exercise engagement was associated with better verbal memory (word-list recall and associative learning; rho = 0.46–0.47; ps FDR < 0.05), and with larger contralateral hippocampal volumes (rho = 0.61; p < 0.01). These effects remained significant when controlling for several clinical and demographic factors. These findings suggest that exercise may be a cognitive reserve factor in TLE, potentially mitigating memory decline by enhancing contralateral hippocampal integrity. With future replication and longitudinal investigation, exercise holds promise as a low-cost and accessible modifiable lifestyle target for improving cognitive health in individuals with refractory TLE

Computational Analysis and Experimental Data Exploring the Role of Hesperetin in Ameliorating ADHD and SIRT1/Nrf2/Keap1/OH-1 Signaling.

Attention deficit hyperactivity disorder (ADHD) manifests as poor attention, hyperactivity, as well as impulsive behaviors. Hesperetin (HSP) is a citrus flavanone with strong antioxidant and anti-inflammatory activities. The present study aimed to test hesperetin efficacy in alleviating experimental ADHD in mice and its influence on hippocampal neuron integrity and sirtuin 1 (SIRT1) signaling. An in silico study was performed to test the related proteins. Groups of mice were assigned as control, ADHD model, ADHD/HSP (25 mg/kg), and ADHD/HSP (50 mg/kg). ADHD was induced by feeding with monosodium glutamate (0.4 g/kg, for 8 weeks) and assessed by measuring the motor and attentive behaviors (open filed test, Y-maze test, and marble burying test), histopathological examination of the whole brain tissues, and estimation of inflammatory markers. The in-silico results indicated the putative effects of hesperetin on ADHD by allowing the integration and analysis of large-scale genomic, transcriptomic, and proteomic data. The in vivo results showed that ADHD model mice displayed motor hyperactivity and poor attention in the behavioral tasks and shrank neurons at various hippocampal regions. Further, there was a decline in the mRNA expression and protein levels for SIRT1, the erythroid 2-related factor-2 (Nrf2), kelch like ECH associated protein 1 (Keap1) and hemeoxygenase-1 (OH-1) proteins. Treatment with HSP normalized the motor and attentive behaviors, prevented hippocampal neuron shrinkage, and upregulated SIRT1/Nrf2/Keap1/OH-1 proteins. Taken together, HSP mainly acts by its antioxidant potential. However, therapeutic interventions with hesperetin or a hesperetin-rich diet can be suggested as a complementary treatment in ADHD patients but cannot be suggested as an ADHD treatment per se as it is a heterogeneous and complex disease.

Protocatechuic Acid from Euonymus alatus Mitigates Scopolamine-Induced Memory Impairment in Mice.

The increasing prevalence of age-related neurodegenerative disorders owing to the aging population worldwide poses substantial challenges. This study investigated the neuroprotective effects of protocatechuic acid (PCA), a compound found in various fruits, vegetables, and grains, using a scopolamine-induced hypomnesia mouse model. Six-week-old male C57BL/6J mice were orally administered PCA at doses of 10 and 100 mg/kg body weight per day for two weeks, along with intraperitoneal injections of scopolamine. Learning and memory abilities were assessed using the passive avoidance, Morris water maze, and Y-maze behavioral assays. Biochemical analyses evaluated the levels of oxidative stress markers, including 8-hydroxydeoxyguanosine (8-OHdG) in the blood and malondialdehyde (MDA) in the brain, as well as phase II antioxidant proteins in the hippocampus. Histological examination was conducted to determine hippocampal integrity. Our results demonstrated that PCA administration at 10 mg/kg body weight per day or higher for two weeks (i) significantly ameliorated scopolamine-induced learning and memory impairments, as evidenced by improved performance in behavioral tasks, (ii) reduced plasma 8-OHdG levels and cerebral MDA levels in a dose-dependent manner, (iii) increased antioxidant protein expressions in the hippocampal tissue, and (iv) mitigated histological damage in the hippocampal region of the brain. These findings suggest that oral administration of PCA provides neuroprotective effects against oxidative stress-induced learning and memory impairments, possibly through upregulating antioxidant machinery. Therefore, PCA may serve as a promising dietary supplement for mitigating cognitive deficits associated with neurodegenerative diseases.

Brain-Bone Crosstalk in a Murine Polytrauma Model Promotes Bone Remodeling but Impairs Neuromotor Recovery and Anxiety-Related Behavior.

Traumatic brain injury (TBI) and long bone fractures are a common injury pattern in polytrauma patients and modulate each other's healing process. As only a limited number of studies have investigated both traumatic sites, we tested the hypothesis that brain-bone polytrauma mutually impacts neuro- and osteopathological outcomes. Adult female C57BL/6N mice were subjected to controlled cortical impact (CCI), and/or osteosynthetic stabilized femoral fracture (FF), or sham surgery. Neuromotor and behavioral impairments were assessed by neurological severity score, open field test, rotarod test, and elevated plus maze test. Brain and bone tissues were processed 42 days after trauma. CCI+FF polytrauma mice had increased bone formation as compared to FF mice and increased mRNA expression of bone sialoprotein (BSP). Bone fractures did not aggravate neuropathology or neuroinflammation assessed by cerebral lesion size, hippocampal integrity, astrocyte and microglia activation, and gene expression. Behavioral assessments demonstrated an overall impaired recovery of neuromotor function and persistent abnormalities in anxiety-related behavior in polytrauma mice. This study shows enhanced bone healing, impaired neuromotor recovery and anxiety-like behavior in a brain-bone polytrauma model. However, bone fractures did not aggravate TBI-evoked neuropathology, suggesting the existence of outcome-relevant mechanisms independent of the extent of brain structural damage and neuroinflammation.

Fasudil alleviates alcohol-induced cognitive deficits and hippocampal morphology injury partly by altering the assembly of the actin cytoskeleton and microtubules

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil’s neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6 J mice were exposed to 30% (v/v, 6.0 g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10 mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules—mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.

Association of dietary and nutritional factors with cognitive decline, dementia, and depressive symptomatology in older individuals according to a neurogenesis-centred biological susceptibility to brain ageing.

Hippocampal neurogenesis (HN) occurs throughout the life course and is important for memory and mood. Declining with age, HN plays a pivotal role in cognitive decline (CD), dementia, and late-life depression, such that altered HN could represent a neurobiological susceptibility to these conditions. Pertinently, dietary patterns (e.g., Mediterranean diet) and/or individual nutrients (e.g., vitamin D, omega 3) can modify HN, but also modify risk for CD, dementia, and depression. Therefore, the interaction between diet/nutrition and HN may alter risk trajectories for these ageing-related brain conditions. Using a subsample (n= 371) of the Three-City cohort-where older adults provided information on diet and blood biobanking at baseline and were assessed for CD, dementia, and depressive symptomatology across 12years-we tested for interactions between food consumption, nutrient intake, and nutritional biomarker concentrations and neurogenesis-centred susceptibility status (defined by baseline readouts of hippocampal progenitor cell integrity, cell death, and differentiation) on CD, Alzheimer's disease (AD), vascular and other dementias (VoD), and depressive symptomatology, using multivariable-adjusted logistic regression models. Increased plasma lycopene concentrations (OR [95% CI] = 1.07 [1.01, 1.14]), higher red meat (OR [95% CI] = 1.10 [1.03, 1.19]), and lower poultry consumption (OR [95% CI] = 0.93 [0.87, 0.99]) were associated with an increased risk for AD in individuals with a neurogenesis-centred susceptibility. Increased vitamin D consumption (OR [95% CI] = 1.05 [1.01, 1.11]) and plasma γ-tocopherol concentrations (OR [95% CI] = 1.08 [1.01, 1.18]) were associated with increased risk for VoD and depressive symptomatology, respectively, but only in susceptible individuals. This research highlights an important role for diet/nutrition in modifying dementia and depression risk in individuals with a neurogenesis-centred susceptibility.

The Association Between Cardiovagal Baroreceptor Sensitivity and Hippocampal Tissue Integrity in Young and Middle-aged Adults

Prior research has investigated the association of cardiovagal baroreceptor sensitivity (BRS) with white matter neuronal integrity and cerebral perfusion using magnetic resonance imaging (MRI) techniques such as diffusion tensor imaging (DTI) and arterial spin labeling (ASL); however, less is known about the association with specific regions of gray matter (i.e, hippocampus) involved in memory formation and recall. MR elastography (MRE) has emerged as a constructive tool for assessing the viscoelastic mechanical properties of the brain which are believed to reflect the microstructural integrity of neuronal tissue. PURPOSE: To investigate the association between cardiovagal BRS and the viscoelastic properties of the brain, with a sub goal of examining how advanced age affects this association. We hypothesized that there would be a positive relation between cardiovagal BRS and hippocampal (HC) viscoelastic properties that strengthens with age, indicating a greater influence of blood pressure control on HC microstructural integrity. Methods: Ten young (Yng, 25 ± 2 years) and ten middle-aged adults (MA, 55 ± 3 years) laid in supine position for 10 minutes while arterial blood pressure (ABP) and heart rate (HR) were measured. R-R intervals and systolic blood pressures were plotted within a linear regression to calculate the spontaneous baroreflex slope. Subjects went in an MRI scanner to measure hippocampal viscoelastic properties using MRE. Results: As expected, we observed a lower cBRS in the middle-aged group compared with young (MA: 12.51±4.41 vs. Yng: 25.21±8.77 ms/mmHg, p≤0.05). There were no significant differences in HC stiffness or damping ratio when comparing between age groups (MA: 3.06±0.32 kPa vs. Yng: 3.02±0.09 kPa, p=0.69; MA: 0.2±0.02 vs. Yng: 0.2±0.03, p=0.56). However, a multiple linear regression with age included as a categorical covariate revealed a trend towards a stronger association between HC stiffness and cBRS in the middle-aged compared to the young group (p=0.07). CONCLUSION: In contrast to our hypothesis, preserved BRS was associated with lower HC stiffness in the middle-aged group; however, the physiological importance of this finding needs to be more completely explored. Our findings indicate that the association between short-term blood pressure regulation via cardiovagal BRS may be more closely linked to HC tissue integrity with advancing age. These mechanisms should be explored in a larger cohort including older individuals. Supported by UD Research Foundation 2020 Pilot Grant and P20GM113125. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Epigenetic regulation by KDM5A mediates the effects of prenatal PM2.5 exposure on hippocampal development and synaptic integrity through the Shh signaling pathway

Prenatal environmental exposure could be an essential health risk factor associated with neurodevelopmental disorders in offspring. However, the exact mechanisms underlying the impact of prenatal PM2.5 exposure on offspring cognition remain unclear. In our recent study using a PM2.5 exposed pregnant mouse model, we observed significant synaptic dysfunction in the hippocampi of the offspring. Concurrently, the epigenetic regulator of KDM5A and the Shh signaling pathway exhibited decreased activities. Significantly, changes in hippocampal KDM5A and Shh levels directly correlated with PM2.5 exposure intensity. Subsequent experiments revealed a marked reduction in the expression of Shh signaling and related synaptic proteins when KDM5A was silenced in cells. Notably, the effects of KDM5A deficiency were reversed significantly with the supplementation of a Shh activator. Furthermore, our findings indicate that Shh activation significantly attenuates PM2.5-induced synaptic impairments in hippocampal neurons. We further demonstrated that EGR1, a transcriptional inhibitor, plays a direct role in KDM5A’s regulation of the Shh pathway under conditions of PM2.5 exposure. Our results suggest that the KDM5A’s inhibitory regulation on the Shh pathway through the EGR1 gene is a crucial epigenetic mechanism underlying the synaptic dysfunction in hippocampal neurons caused by maternal PM2.5 exposure. This emphasizes the role of epigenetic regulations in neurodevelopmental disorders caused by environmental factors.

Rosmarinus officinalis extract ameliorates cognitive deficits and hippocampal neurogenesis in mice model of diabetes mellitus

RationaleDiabetes mellitus causes cognitive impairment and negatively affects the hippocampal integrity and neurogenesis. The impaired insulin activity and secretion contribute to the down-regulation of fibroblast growth factor which is an important stimulant of the neurogenic process. The present study elucidated the potential effects of Rosmarinus officinalis, (R. officinalis) on spatial memory and adult hippocampal neurogenesis in diabetic mice model using behavioral tests, histological and immunohistochemical analysis. Material and methodsThe male Balb/c mice were administered a high-fat diet and streptozotocin (STZ) (100 mg/kg i.p.) at 6th and 9th week of age. Following that, 36 h after second dose of STZ, 50 mg/kg R. officinalis extract was administered orally for 21 days. ResultsSTZ and a high-fat diet caused diabetes that led to the defects in learning and memory and compromised the process of hippocampal neurogenesis. Interestingly, R. officinalis improved cognitive functions and increased the expression of neurogenic markers including KI67 and NeuN, suggesting an improvement in the process of adult hippocampal neurogenesis. ConclusionsIt has been suggested that R. officinalis may act as a potential agent for the improvement of neurodegeneration and learning and memory deficits associated with diabetes. These findings warrant further investigation of the specific active constituents of R. officinalis involved in the regulation of these molecular processes to be considered as novel adjunctive therapy for diabetes mellitus-associated neurological consequences.

Preoperative recovery sleep ameliorates postoperative cognitive dysfunction aggravated by sleep fragmentation in aged mice by enhancing EEG delta-wave activity and LFP theta oscillation in hippocampal CA1

Sleep fragmentation (SF) is a common sleep problem experienced during the perioperative period by older adults, and is associated with postoperative cognitive dysfunction (POCD). Increasing evidence indicates that delta-wave activity during non-rapid eye movement (NREM) sleep is involved in sleep-dependent memory consolidation and that hippocampal theta oscillations are related to spatial exploratory memory. Recovery sleep (RS), a self-regulated state of sleep homeostasis, enhances delta-wave power and memory performance in sleep-deprived older mice. However, it remains unclear whether RS therapy has a positive effect on cognitive changes following SF in older mouse models. Therefore, this study aimed to explore whether preoperative RS can alleviate cognitive deficits in aged mice with SF. A model of preoperative 24-h SF combined with exploratory laparotomy-induced POCD was established in 18-month-old mice. Aged mice were treated with preoperative 6-h RS following SF and postoperative 6-h RS following surgery, respectively. The changes in hippocampus-dependent cognitive function were investigated using behavioral tests, electroencephalography (EEG), local field potential (LFP), magnetic resonance imaging, and neuromorphology. Mice that underwent 24-h SF combined with surgery exhibited severe spatial memory impairment; impaired cognitive performance could be alleviated by preoperative RS treatment. In addition, preoperative RS increased NREM sleep; enhanced EEG delta-wave activity and LFP theta oscillation in the hippocampal CA1; and improved hippocampal perfusion, microstructural integrity, and neuronal damage. Taken together, these results provide evidence that preoperative RS may ameliorate the severity of POCD aggravated by SF by enhancing delta slow-wave activity and hippocampal theta oscillation, and by ameliorating the reduction in regional cerebral blood flow and white matter microstructure integrity in the hippocampus.

Mechanical pain sensitivity is associated with hippocampal structural integrity.

Rodents and human studies indicate that the hippocampus, a brain region necessary for memory processing, responds to noxious stimuli. However, the hippocampus has yet to be considered a key brain region directly involved in the human pain experience. One approach to answer this question is to perform quantitative sensory testing on patients with hippocampal damage-ie, medial temporal lobe epilepsy. Some case studies and case series have performed such tests in a handful of patients with various types of epilepsy and have reported mixed results. Here, we aimed to determine whether mechanical pain sensitivity was altered in patients diagnosed with temporal lobe epilepsy. We first investigated whether mechanical pain sensitivity in patients with temporal lobe epilepsy differs from that of healthy individuals. Next, in patients with temporal lobe epilepsy, we evaluated whether the degree of pain sensitivity is associated with the degree of hippocampal integrity. Structural integrity was based on hippocampal volume, and functional integrity was based on verbal and visuospatial memory scores. Our findings show that patients with temporal lobe epilepsy have lower mechanical pain sensitivity than healthy individuals. Only left hippocampal volume was positively associated with mechanical pain sensitivity-the greater the hippocampal damage, the lower the sensitivity to mechanical pain. Hippocampal measures of functional integrity were not significantly associated with mechanical pain sensitivity, suggesting that the mechanisms of hippocampal pain processing may be different than its memory functions. Future studies are necessary to determine the mechanisms of pain processing in the hippocampus.

Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index.

Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity. Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable. Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI). These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.

Hippocampal resting-state connectivity is associated with posterior-cortical cognitive impairment in Parkinson's disease.

Frontal and posterior-cortical cognitive subtypes in Parkinson's disease (PD) present with executive/attention and memory/visuospatial deficits, respectively. As the posterior-cortical subtype is predicted to progress rapidly toward dementia, the present study aimed to explore biological markers of this group using resting-state functional magnetic resonance imaging (rs-fMRI). K-means cluster analysis delineated subtypes (cognitively intact, frontal, posterior-cortical, and globally impaired) among 85 people with PD. A subset of PD participants (N=42) and 20 healthy controls (HCs) underwent rs-fMRI. Connectivity of bilateral hippocampi with regions of interest was compared between posterior-cortical, cognitively intact, and HC participants using seed-based analysis, controlling for age. Exploratory correlations were performed between areas of interest from the group analysis and a series of cognitive tests. The posterior-cortical subtype (N=19) showed weaker connectivity between the left hippocampus and right anterior temporal fusiform cortex compared to the cognitively intact (N=11) group, p-false discovery rate (FDR)=.01, and weaker connectivity between bilateral hippocampi and most fusiform regions compared to HCs (N=20). No differences were found between HCs and cognitively intact PD. Exploratory analyses revealed strongest associations between connectivity of the right anterior temporal fusiform cortex and left hippocampus with category fluency (p-FDR=.01). Results suggest that weakened connectivity between the hippocampus and fusiform region is a unique characteristic of posterior-cortical cognitive deficits in PD. Further exploration of hippocampal and fusiform functional integrity as a marker of cognitive decline in PD is warranted.

Melatonin Modulates Cell Cycle Dynamics and Promotes Hippocampal Cell Proliferation After Ischemic Injury in Neonatal Rats

Promoting neural cell proliferation may represent an important strategy for enhancing brain repair after developmental brain injury. The present study aimed to assess the effects of melatonin on cell proliferation after an ischemic injury in the developing hippocampus, focusing on cell cycle dynamics. After in vivo neonatal hypoxia–ischemia (HI), hippocampal cell cycle dynamics were assessed by flow cytometry, together with histological evaluation of dentate gyrus cellularity and proliferation. Melatonin significantly increased the number of proliferating cells in the G2/M phase as well as the proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) labeling reduced by HI. In vivo BrdU labeling revealed a higher BrdU-positivity in the dentate gyrus of ischemic rats treated with melatonin, an effect followed by increased cellularity and preserved hippocampal tissue integrity. These results indicate that the protective effect of melatonin after ischemic injury in neonatal rats may rely on the modulation of cell cycle dynamics of newborn hippocampal cells and increased cell proliferation.

Association Between Hippocampal Volumes and Cognition in Cerebral Amyloid Angiopathy.

Accumulating evidence suggests that gray matter atrophy, often considered a marker of Alzheimer disease (AD), can also result from cerebral small vessel disease (CSVD). Cerebral amyloid angiopathy (CAA) is a form of sporadic CSVD, diagnosed through neuroimaging criteria, that often co-occurs with AD pathology and leads to cognitive impairment. We sought to identify the role of hippocampal integrity in the development of cognitive impairment in a cohort of patients with possible and probable CAA. Patients were recruited from an ongoing CAA study at Massachusetts General Hospital. Composite scores defined performance in the cognitive domains of memory, language, executive function, and processing speed. Hippocampal subfields' volumes were measured from 3T MRI, using an automated method, and multivariate linear regression models were used to estimate their association with each cognitive domain and relationship to CAA-related neuroimaging markers. One hundred twenty patients, 36 with possible (age mean [range]: 75.6 [65.6-88.9]), 67 with probable CAA (75.9 [59.0-94.0]), and 17 controls without cognitive impairment and CSVD (72.4 [62.5-82.7]; 76.4% female patients), were included in this study. We found a positive association between all investigated hippocampal subfields and memory and language, whereas specific subfields accounted for executive function (CA4 [Estimate = 5.43; 95% CI 1.26-9.61; p = 0.020], subiculum [Estimate = 2.85; 95% CI 0.67-5.02; p = 0.022]), and processing speed (subiculum [Estimate = 1.99; 95% CI 0.13-3.85; p = 0.036]). These findings were independent of other CAA-related markers, which did not have an influence on cognition in this cohort. Peak width of skeletonized mean diffusivity (PSMD), a measure of white matter integrity, was negatively associated with hippocampal subfields' volumes (CA3 [Estimate = -0.012; 95% CI -0.020 to -0.004; p = 0.034], CA4 [Estimate = -0.010; 95% CI -0.020 to -0.0007; p = 0.037], subiculum [Estimate = -0.019; 95% CI -0.042 to -0.0001; p = 0.003]). These results suggest that hippocampal integrity is an independent contributor to cognitive impairment in patients with CAA and that it might be related to loss of integrity in the white matter. Further studies exploring potential causes and directionality of the relationship between white matter and hippocampal integrity may be warranted.

Sex differences in region-specific hippocampal areas in Alzheimer’s Disease: an animal-based approach

Background: Atrophy in the hippocampus is responsible for memory and cognitive decline in Alzheimer’s Disease (AD). Progression and presentation of AD in men and women are different, and the hippocampus and its subregions could be affected differently. By identifying what areas of the hippocampus are affected by sex, diagnostic tools can be better used to clinically identify and treat AD.&#x0D; Aims: The goals of the proposed research are: (1) use in vivo MRI techniques to isolate the hippocampus in a mouse model, (2) use data analysis to compare the volume of the hippocampus and its subregions in 5xFAD mice, and (3) see if sex plays a role in differing hippocampal volume, and (4) assess the translational utility of using structural MRI to measure hippocampal integrity for future in vivo human brain studies/clinical practice.&#x0D; Methods: We used the imaging software FSLeyes to examine MRI images and isolate hippocampal subregion masks. MRI images were taken at the 2-month age period when amyloid-B deposition begins in the forebrain. Upon isolation of the hippocampal mask of each MRI, group classification was identified, and quantitative analysis was performed to compare groups.&#x0D; Results: We found significant lower spatial volume in Stratum Granulosum (SG) of the hippocampus in female mice compared to male mice. The SG contains dentate granule cells, responsible for spatial memory. Apart from this, the data that we obtained was nonsignificant but did show that female mice contained mainly smaller hippocampus subregions and total volumes despite TICV being larger in females.&#x0D; Conclusion and Impact: More data is needed to observe the degeneration of SG over a lifetime and assess if it is the reason why males retain spatial memory in AD as opposed to females. Otherwise, analyzing hippocampal volume in the early stages of AD doesn’t appear to be sufficient in explaining outstanding sex differences in AD presentation and progression.

Demands on perceptual and mnemonic fidelity are a key determinant of age-related cognitive decline throughout the lifespan.

Aging results in less detailed memories, reflecting reduced fidelity of remembered compared to real-world representations. We tested whether poorer representational fidelity across perception, short-term memory (STM), and long-term memory (LTM) are among the earliest signs of cognitive aging. Our paradigm probed target-lure object mnemonic discrimination and precision of object-location binding. Across the lifespan, cognitive deficits were observed in midlife when detailed stimulus representations were required for perceptual and short/long-term forced choice mnemonic discrimination. A continuous metric of object-location source memory combined with computational modeling demonstrated that errors in STM and LTM in middle-aged adults were largely driven by a loss of precision for retrieved memories, not necessarily by forgetting. On a trial-by-trial basis, fidelity of item and spatial information was more tightly bound in LTM compared to STM with this association being unaffected by age. Standard neuropsychological tests without demands on memory quality (digit span, verbal learning) were less sensitive to age effects than STM and LTM precision. Perceptual discrimination predicted mnemonic discrimination. Neuropsychological proxies for prefrontal executive functions correlated with STM, but not LTM fidelity. Conversely, neuropsychological indicators of hippocampal integrity correlated with mnemonic discrimination and precision of both STM and LTM, suggesting partially dissociable mechanisms of interindividual variability in STM and LTM fidelity. These findings suggest that reduced representational fidelity is a hallmark of cognitive aging across perception, STM, and LTM and can be observed from midlife onward. Continuous memory precision tasks may be promising for the early detection of subtle age-related cognitive decline. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Resveratrol showed anti-inflammatory effects on hippocampus via suppressing NFκB.

Traumatic brain injury (TBI) is the damage to the brain caused by external blow or jolt to the head or body. TBI secondarily induces cell damage in the hippocampus. This study aimed to investigate effects of resveratrol treatment histological examination and nuclear factor kappa B (NFκB) expression in hippocampus after TBI. Twenty-four rats were assigned to three groups: sham, TBI and TBI+Resveratol. TBI was conducted by dropping a 50-g weight from a 1-meter height from a tube to the head of animals. 20 mg/kg resveratrol was orally administered to rats after TBI. Blood was collected to measure malondialdehyde (MDA) and glutathione (GSH) contents. Cerebral tissues were processed for histopathology and furtherly for immunohistochemical analysis. MDA content was significantly increased and GSH value were significantly decreased in TBI group compared to sham group. Resveratrol treatment significantly improved biochemical scores in TBI+Resveratrol group. Normal histological appearance was observed in hippocampal sections of sham group. In TBI group, neurons in hippocampus were degenerated. Their nuclei were pyknotic. Other neurons and supportive neuroglial cells in hippocampal proper and dentate gyrus were also disrupted. Hippocampal proper integrity was lost with vascular dilatation. NFκB was upregulated in hippocampal neurons of TBI group. Resveratrol treatment alleviated pathologies and downregulated NFκB expression in hippocampus. TBI caused adverse alterations in free radicals' balance system and histological structures of hippocampus. Resveratrol with its antioxidant and anti-inflammatory effects reduced the damage caused by TBI.