Neurochemical Markers Research Articles

Development of neurochemical labeling in the intermediolateral nucleus of cats' spinal cord.

NeuN is a neuron-specific nuclear protein expressed in most mature neuronal cell types, with some exceptions. These exceptions are known mainly for the brain but not for the spinal cord or the spinal visceral networks for which only scarce information is available. One of the most defined visceral structures in the spinal cord is the sympathetic intermediolateral nucleus located within the thoracolumbar segments. We investigated the NeuN staining in the intermediolateral nucleus and compared it with the staining for two neurochemical markers of visceral neurons: nitric oxide synthase and calcium-binding protein calretinin in adult cats and in kittens aged 0, 14, and 35 days. A clear NeuN-immunonegativity was obtained for intermediolateral neurons labeled for nitric oxide synthase for both adult cats and kittens. In contrast, a matched immunopositivity for the NeuN and calretinin was obtained, showing an age-dependent degree of this colocalization, which was high in newborn kittens, decreased on postnatal 14 and 35 days and persisted at a moderate level up to adulthood. Perhaps our data displayed a heterogeneity of the intermediolateral neurons.

Selective Optogenetic Dopamine Terminal Stimulation Reveals Role of GABAergic Signaling in Individual Differences in Dopamine Release

An estimated 70.5% of Americans aged 12 or older report having used an illicit substance at least once, while about 10‐20% of those individuals ultimately develop a substance use disorder (SUD). These data highlight substantial individual variability in the risk of developing SUD following initial drug use. Identifying markers of increased risk provides a significant opportunity to identify at‐risk populations and to aid in the prevention of the development of SUD. In preclinical rodent models, locomotor response to a novel environment predicts drug use vulnerability. Rodents that demonstrate higher locomotor response to an inescapable novel environment (high responders; HR) acquire self‐administration (SA) of drugs more rapidly and at lower doses compared to low responders (LR). Striatal dopamine (DA) signaling is critical for the acquisition of drug SA and tonic/phasic firing patterns of DA neurons encode information about salient environmental stimuli and rewards. HR rats show increased phasic DA signaling to reward‐predictive cues compared to LR rats. Dopamine release dynamics are tightly controlled by local modulation within the nucleus accumbens (NAc), including by nicotinic acetylcholine receptors (nAChRs), but the mechanisms by which this local modulation may contribute to differential DA release is not fully understood. Our lab has previously shown that locomotor response to a novel environment predicts nAChR modulation of phasic DA signals in the NAc. Specifically, desensitization or blockade of α6β2‐containing (α6β2*) nAChRs within the NAc was found to augment phasic DA signals in brain slices of HR rats, and reduce phasic DA signals in LR rats. However, these studies utilized non‐specific electrical stimulation to record DA release. In the present study, we used ex vivo fast‐scan cyclic voltammetry with an optogenetic approach to selectively stimulate DA neuron terminals or cholinergic interneurons (CINs) within the NAc to examine the specific contributions of acetylcholine (ACh) to the overall DA response in HR and LR rats. We find that, contrary to previous results with electrical stimulation, selective DA phasic stimulation results in lower DA release in HRs compared to LRs, while blockade of α6β2* nAChRs using light stimulation results in higher DA release in HRs. This suggests that additional circuitry is likely involved in differential DA signaling within the NAc. Given the tonic activity of CINs and presence of nAChRs on GABA interneurons, we next used pharmacological manipulations to examine the possibility of GABA signaling contributing to individual differences in DA release. Here, we find that antagonism of GABA receptors blocks the previously seen differential effects of α6β2* nAChR antagonism on DA release, suggesting that GABA interneurons do play a critical role in differential DA signaling in HRs versus LRs. In sum, these data help form a clearer understanding of the mechanisms underlying individual differences in DA signaling, which may be a primary driver of differences in sensitivity to the reinforcing effects of drugs of abuse. Investigating these mechanisms allows us to better identify behavioral and neurochemical markers of SUD vulnerability in humans and to ultimately stimulate development of individualized and effective treatments.

Leveraging a translational research approach to drive diagnostic and treatment advances for autism.

Autism spectrum disorder (ASD) is a prevalent and poorly understood neurodevelopmental disorder. There are currently no laboratory-based diagnostic tests to detect ASD, nor are there any disease-modifying medications that effectively treat ASD’s core behavioral symptoms. Scientific progress has been impeded, in part, by overreliance on model organisms that fundamentally lack the sophisticated social and cognitive abilities essential for modeling ASD. We therefore saw significant value in studying naturally low-social rhesus monkeys to model human social impairment, taking advantage of a large outdoor-housed colony for behavioral screening and biomarker identification. Careful development and validation of our animal model, combined with a strong commitment to evaluating the translational utility of our preclinical findings directly in patients with ASD, yielded a robust neurochemical marker (cerebrospinal fluid vasopressin concentration) of trans-primate social impairment and a first-in-class medication (intranasal vasopressin) shown in a small phase 2a pilot trial to improve social abilities in children with ASD. This translational research approach stands to advance our understanding of ASD in a manner not readily achievable with existing animal models, and can be adapted to investigate a variety of other human brain disorders which currently lack valid preclinical options, thereby streamlining translation and amplifying clinical impact more broadly.

Preventive Efficiency of Chelidonium majus Ethanolic Extract Against Aflatoxin B1 Induced Neurochemical Deteriorations in Rats.

<b>Background and Objective:</b> Aflatoxins affect many species including humans and animals, therefore the present study was designed to investigate the protective effect of <i>Chelidonium majus</i> Ethanolic Extract (CMEE) on neurotoxicity induced by Aflatoxin B<sub>1</sub> (AFB1) in rats. <b>Materials and Methods:</b> Four groups of male Albino rats were treated orally for 28 days as follows: (1) Control group was daily given DMSO-PBS buffer (1.0 mL per rat), (2) CMEE (300 mg kg<sup>1</sup>/day) dissolved in DMSO-PBS buffer, (3) AFB1 (80 μg kg<sup>1</sup>/day) dissolved in DMSO-PBS buffer and (4) Received daily AFB1 (300 mg kg<sup>1</sup>) in combination with CMEE (300 mg kg<sup>1</sup>). <b>Results:</b> CMEE exhibits antioxidant activity <i>in vitro</i> and neuroameliorative efficiency <i>in vivo</i> as its administration in combination with AFB1 succeeded significantly in down regulating the elevated levels of inflammatory and apoptotic markers and restoring the values of neurochemical markers (AChE-ase, dopamine and serotonin) that were deteriorated by AFB1 intake. <b>Conclusion:</b> In conclusion, the neuroprotective effect of CMEE may be mediated through its antioxidant and free radical scavenging activity that proved from the data<i> </i>of ferric-reducing power ability and DPPH radical scavenging activity.

Dihydroquercetin improves rotenone-induced Parkinsonism by regulating NF-κB-mediated inflammation pathway in rats.

This study examined the effect of dihydroquercetin (DHQ), also knofigurewn as taxifolin, on rotenone-induced Parkinsonism in rats. Male Wistar rats were administered 1.5 mg/kg rotenone for 10 days and subsequently treated with 0.25-1.0 mg/kg DHQ for 3 days followed by the assessment of parkinsonian symptoms. Brain striatal redox stress and neurochemical dysfunction markers were assessed spectrophotometrically. Histopathological evaluation of the striatum was done by hematoxylin and eosin staining technique. The expression of genes involved in the activation of NF-κB signaling pathway (IL-1β, TNF-α, NF-κB and IκKB), and the p53 gene in the striatum were determined by RT-qPCR. DHQ attenuated parkinsonian symptoms as well as striatal redox stress, neurochemical dysfunction, and histological alterations occasioned by rotenone toxicity. Importantly, DHQ significantly suppressed the rotenone-induced upregulation of IL-1β, NF-κB, and IκKB expression (p < 0.05) in the striatum of parkinsonian rats. DHQ demonstrated notable neurotherapeutic potential against rotenone-induced Parkinsonism in rats by improving parkinsonian symptoms (bradykinesia, catalepsy, postural instability, impaired locomotor behavior, and tremor) and neurochemical dysfunctions via modulation of genes involved in the activation of the canonical pathway of NF-κB-mediated inflammation.

Aerobic Exercise Mediated Increase in BDNF Expression Ameliorates Depression in Propylthiouracil-Induced Hypothyroidism in Adult Rats.

• Hypothyroidism is associated with depressive symptoms. • Swimming exercise for 4 weeks alleviated depressive behavior in hypothyroid rats. • The enhanced irisin/BDNF axis activity following moderate aerobic exercise was positively correlated with climbing time in forced swimming test and with brain serotonergic system activity. • It is concluded that moderate aerobic exercise alleviated hypothyroidism-associated depression via increased BDNF expression. : The prevalence of depression with hypothyroidism is high. : To study the ability of aerobic exercise to improve hypothyroidism associated depression and to explore the underlying mechanisms. 21 adult male rats, allocated in three groups; Euthyroid, Hypothyroid (oral propyl-thiouracil for 45 days), Exercise-treated hypothyroid group (30 minutes, swimming, 4 weeks). Forced swim test and histopathological brain examination were performed. Serum free T3, T4, TSH, irisin, brain neurochemical, oxidant-antioxidant and apoptotic markers were measured . : Swimming exercise increased serum T3, T4, climbing and swimming times, brain serotonin, BDNF expression, glutathione peroxidase, antiapoptotic Bcl-2 and serum irisin levels and decreased TSH, immobility time, MDA, BAX/Bcl-2 ratio. Climbing time was positively correlated with BDNF, serotonin and T3. : Moderate aerobic exercise alleviated hypothyroidism-associated depression, via increased BDNF expression, which enhances hippocampal neurogenesis, serotonergic system activity and combat neuronal apoptosis.

Study of Neuropeptide Substance P as A Marker of Pain in Newborn Infant

BACKGROUND: Prolonged and repeated untreated pain in newborn infant may produce a relatively permanent adverse long-term sequela. AIM: The aim of this study was to evaluate the potential role for neuropeptides substance P (SP) as neurochemical pain marker in newborn infants in order to decrease unnecessary use of analgesics and protect the developing brain. METHODS: This case-control study was conducted on 60 newborn infants. They were assigned to four groups, control preterm, sick preterm, control full term, and sick full term. All neonates were subjected to estimation of pain through neonatal infants pain score (NIPS) as well as Neuropeptide SP on the 1st and 5th day of life. The NIPS addresses five behavioral parameters (facial expression, crying, arm movement, leg movement, and state arousal) and one physiological parameter (breathing pattern). Results were further evaluated according to nature of the procedures; invasive and non-invasive procedures. RESULTS: There was a significant increase in the severity of pain score among the sick preterm and full-term infants after invasive procedures. There was a significant increase in SP in the sick preterm group than the control preterm on the 1st and 5th day of life; p were =0.003 and = 0.037, while full-term infants showed significant increase on the 5th day; p = 0.005. Furthermore, there was no significant difference in SP values between the preterm and full-term infants on the 1st and 5th day of life. SP increased significantly after invasive procedures than noninvasive procedures in the sick full-term and sick preterm infants weather in the 1st or 5th day of life. There was a significant correlation between the pain score NIPS and SP level on the 1st day of life. CONCLUSION: SP can be used as pain marker in sick preterm and full-term newborn infants. It showed increase with invasive procedures, acute and chronic pain.

Cerebrospinal fluid levels of L-glutamate signal central inflammatory neurodegeneration in multiple sclerosis.

Excessive extracellular concentrations of L-glutamate (L-Glu) can be neurotoxic and contribute to neurodegenerative processes in multiple sclerosis (MS). The association between cerebrospinal fluid (CSF) L-Glu levels, clinical features, and inflammatory biomarkers in patients with MS remains unclear. In 179MS patients (relapsing remitting, RR, N=157; secondary progressive/primary progressive, SP/PP, N=22), CSF levels of L-Glu at diagnosis were determined and compared with those obtained in a group of 40 patients with non-inflammatory/non-degenerative disorders. Disability at the time of diagnosis, and after 1year follow-up, was assessed using the Expanded Disability Status Scale (EDSS). CSF concentrations of lactate and of a large set of pro-inflammatory and anti-inflammatory molecules were explored. CSF levels of L-Glu were slightly reduced in MS patients compared to controls. In RR-MS patients, L-Glu levels correlated with EDSS after 1year follow-up. Moreover, in MS patients, significant correlations were found between L-Glu and both CSF levels of lactate and the inflammatory molecules interleukin (IL)-2, IL-6, and IL-1 receptor antagonist. Altered expression of L-Glu is associated with disability progression, oxidative stress, and inflammation. These findings identify CSF L-Glu as a candidate neurochemical marker of inflammatory neurodegeneration in MS.

Mechanisms of neurogenesis and angiogenesis in ischaemic stroke: literature review

Scientific achievements of recent decades indicate that neurogenesis and angiogenesis are interrelated processes in the struggle for functional recovery after ischaemic stroke. This literature review presents current data on the neurovascular interactions in ischaemic stroke, and describes the role of signalling molecules and growth factors in the regulation of neurogenesis and angiogenesis, which are crucial for neuronal survival and neuroplasticity. The authors conducted a literature search for abnormal neuroblast migration into the ischaemic penumbra and the role of signalling molecules, molecular targets of angiogenesis, and role of endogenous growth factors and neurochemical markers in post-stroke vascular regulation in acute cerebral ischaemia. Relevant keywords were entered into the PubMed and Google Scholar search engines, as well as Scopus, Web of Science, MedLine, The Cochrane Library, EMBASE, Global Health, CyberLeninka, eLibrary, and other databases.&#x0D; Despite promising results obtained in animal models, and the data from clinical studies, deeper interrelationships between molecular and cellular interactions of neurogenesis and angiogenesis are still not entirely clear. Further study and understanding of complex interactions between neurogenesis and angiogenesis is needed to find targets for exogenous growth factor administration and changes in endogenous molecule expression for treatment of ischaemic brain injury.

Decreased thalamo-cortico connectivity during an implicit sequence motor learning task and 7\xa0days escitalopram intake

Evidence suggests that selective serotonin reuptake inhibitors (SSRIs) reorganize neural networks via a transient window of neuroplasticity. While previous findings support an effect of SSRIs on intrinsic functional connectivity, little is known regarding the influence of SSRI-administration on connectivity during sequence motor learning. To investigate this, we administered 20 mg escitalopram or placebo for 1-week to 60 healthy female participants undergoing concurrent functional magnetic resonance imaging and sequence motor training in a double-blind randomized controlled design. We assessed task-modulated functional connectivity with a psycho-physiological interaction (PPI) analysis in the thalamus, putamen, cerebellum, dorsal premotor, primary motor, supplementary motor, and dorsolateral prefrontal cortices. Comparing an implicit sequence learning condition to a control learning condition, we observed decreased connectivity between the thalamus and bilateral motor regions after 7 days of escitalopram intake. Additionally, we observed a negative correlation between plasma escitalopram levels and PPI connectivity changes, with higher escitalopram levels being associated with greater thalamo-cortico decreases. Our results suggest that escitalopram enhances network-level processing efficiency during sequence motor learning, despite no changes in behaviour. Future studies in more diverse samples, however, with quantitative imaging of neurochemical markers of excitation and inhibition, are necessary to further assess neural responses to escitalopram.

Gucy2d selectively marks inhibitory dynorphin neurons in the spinal dorsal horn but is dispensable for pain and itch sensitivity.

Inhibitory neurons in the spinal dorsal horn can be classified based on expression of neurochemical marker genes. However, these marker genes are often expressed throughout the central nervous system, which poses challenges for manipulating genetically identified spinal neurons without undesired off-target effects. We investigated whether Gucy2d, previously identified as a highly selective marker of dynorphin-lineage neurons in the dorsal horn, is expressed in other locations within the adult mouse spinal cord, dorsal root ganglia (DRG), or brain. In addition, we sought to molecularly characterize Gucy2d-expressing dorsal horn neurons and investigate whether the disruption of Gucy2d gene expression affects sensitivity to itch or pain. In situ hybridization experiments assessed Gucy2d mRNA expression in the adult mouse spinal cord, DRG, and brain, and its colocalization with Pax2, Bhlhb5, and Pde2a in dorsal horn neurons. Knockout mice lacking Gucy2d expression were compared with littermate controls to assess sensitivity to chloroquine-induced itch and dry skin-mediated chronic itch, as well as heat, cold, or mechanical stimuli. Gucy2d is selectively expressed in dynorphin-lineage neurons in lamina I-III of the adult mouse spinal cord but not in the brain or DRG. Spinal Gucy2d-expressing neurons are inhibitory neurons that also express the transcription factor Bhlhb5 and the cGMP-dependent phosphodiesterase Pde2a. Gucy2d knockout mice did not exhibit altered responses to itch or pain. The selective expression of Gucy2d within a subpopulation of inhibitory dorsal horn neurons may yield a means to selectively manipulate inhibitory signaling at the level of the spinal cord without effects on the brain.

Long-term quality of life of cancer survivors: A case-control study.

12077 Background: There were extensive reports in literature about the debilitating health experienced by cancer patients during treatment. This study examined how the quality of life of cancer survivors changed over time. Methods: The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of adults and children in the U.S. This study involved participants in NHANES from 2000-2020. Participants who reported having had a cancer diagnosis were matched one to one with participants who reported no cancer diagnosis by age, gender, race, year of recruitment into NHANES, and comorbidities. Quality of life measures including self-reported general/physical/mental health, examinations, and laboratory tests were compared between cancer cases and matched controls using paired t tests. Results: This study included 5,166 pairs of cancer cases and matched controls. Mean age was 66 (±15 years). Male 47% and female 53%. White 69%, Black 14%, Hispanic 12%, others 5%. Most common comorbidities were hypertension (56%), arthritis (50%), diabetes (19%), and thyroid (18%). About 38% of cancer cases had survived in 1-5 years; 22% in 6-10 years; 39% in 10+ years. Most prevalent cancers were skin (28%), breast (15%), and prostate (15%). Compared to controls, cancer cases who had survived in 1-5 years reported higher rates of poor general health (38% vs. 27%, p &lt;.0001), hospitalizations (31% vs. 17%, p &lt;.0001), mental health visits (9% vs. 7%, p =.0204). There were no significant differences in general health and healthcare utilization between cancer cases who survived &gt; 5 years and controls. There were no clinically meaningful differences in laboratory tests and examinations between cancer cases and controls regardless of survival time. Conclusions: During the first 5 years after cancer diagnosis, survivors reported worse health than controls. As survival time extended, there was no difference between cancer cases and controls. The debilitating health reported during the first 5 years could not be explained by examinations and laboratory tests alone. Future research should explore neurochemical and hormonal markers to investigate adverse effects of cancer treatment on long-term quality of life.

Response to Novelty Predicts α7 Nicotinic Receptor and Voltage‐Gated Calcium Channel Modulation of Dopamine Release

An estimated 70.5% of Americans aged 12 or older report having used an illicit substance at least once, while about 10-20% of those individuals ultimately develop a substance use disorder (SUD). These data highlight substantial individual variability in the risk of developing SUD following initial drug use. Identifying markers of increased risk provides a significant opportunity to identify at-risk populations and to aid in the prevention of the development of SUD. In preclinical rodent models, locomotor response to a novel environment predicts drug use vulnerability. Rodents that demonstrate higher locomotor response to an inescapable novel environment (high responders; HR) acquire self-administration (SA) of drugs more rapidly and stably compared to low responders (LR). Striatal dopamine (DA) signaling is critical for the acquisition of drug SA and tonic/phasic firing patterns of DA neurons encode information about salient environmental stimuli and rewards. HR rats show increased phasic DA signaling to reward-predictive cues compared to LR rats. Dopamine release dynamics are tightly controlled by local modulation within the nucleus accumbens (NAc), including through glutamatergic signaling and modulation by nicotinic acetylcholine receptors (nAChRs), but the mechanisms by which this local modulation may contribute to differential DA release is not fully understood. Our lab has previously shown that locomotor response to a novel environment predicts nAChR modulation of phasic DA signals in the NAc. Specifically, desensitization or blockade of α6β2-containing nAChRs within the NAc was found to augment phasic DA signals in brain slices of HR rats, and reduce phasic DA signals in LR rats. However, other nAChR subtypes may also contribute to individual differences in DA signaling, including α7 nAChRs localized to striatal glutamate terminals. In the present study, we used ex vivo fast-scan cyclic voltammetry to examine how antagonism of α7 nAChRs impacts DA release across a range of stimulation frequencies in the NAc of HR and LR animals and examine what mechanisms may be mediating this effect. We find that modulation of DA release by α7 nAChRs can be predicted by response to novelty at phasic-like stimulations. Given the role that nAChRs play in calcium (Ca2+) entry into the cell, we additionally tested the possibility that differential Ca2+ utilization is one mechanism underlying differential DA modulation by nAChRs and utilized pharmacological manipulations to test possible voltage-gated Ca2+ channel (VGCC) subtype-specific effects. Here, we demonstrate that lowered Ca2+ concentration unmasks a diverging DA release profile between HRs and LRs at phasic-like stimulation frequencies and find that P/Q-type VGCCs appear to drive these individual differences in Ca2+ utilization. In sum, these data help form a more coherent understanding of the mechanisms underlying individual differences in vulnerability. Investigating these mechanisms allows us to better identify behavioral and neurochemical markers of substance abuse risk in humans and to ultimately stimulate development of more individualized and effective treatments.

Spinal Inhibitory Interneurons: Gatekeepers of Sensorimotor Pathways.

The ability to sense and move within an environment are complex functions necessary for the survival of nearly all species. The spinal cord is both the initial entry site for peripheral information and the final output site for motor response, placing spinal circuits as paramount in mediating sensory responses and coordinating movement. This is partly accomplished through the activation of complex spinal microcircuits that gate afferent signals to filter extraneous stimuli from various sensory modalities and determine which signals are transmitted to higher order structures in the CNS and to spinal motor pathways. A mechanistic understanding of how inhibitory interneurons are organized and employed within the spinal cord will provide potential access points for therapeutics targeting inhibitory deficits underlying various pathologies including sensory and movement disorders. Recent studies using transgenic manipulations, neurochemical profiling, and single-cell transcriptomics have identified distinct populations of inhibitory interneurons which express an array of genetic and/or neurochemical markers that constitute functional microcircuits. In this review, we provide an overview of identified neural components that make up inhibitory microcircuits within the dorsal and ventral spinal cord and highlight the importance of inhibitory control of sensorimotor pathways at the spinal level.

Consciousness, Anesthesia, and Acetylcholine.

Consciousness, Anesthesia, and Acetylcholine.

Beta-synuclein in cerebrospinal fluid as an early diagnostic marker of Alzheimer’s disease

ObjectiveSynaptic loss plays a major role in Alzheimer’s disease (AD). However so far no neurochemical marker for synaptic loss has been introduced into clinical routine. By mass spectrometry beta-synuclein was...

Oral administration of Byrophyllum pinnatum flavonoid ameliorates cognitive impairment via modulating cortical neurochemicals and oxidative stress in aluminum chloride‐induced Alzheimer’s disease‐like condition in wistar rats

AbstractBackgroundAluminum, a potent neurotoxicant is a major risk factor involved in the perturbation of neurochemicals leading to the development and progression of Alzheimer’s disease. Byrophyllum pinnatum is widely distributed in Southern Nigeria and used locally for the treatment of various ailments including neurological disorders. This study was aimed to access the neuro restorative potential of B. pinnatum flavonoids (BPF) in aluminum chloride (AlCl3)‐induced AD‐like condition in Wistar ratsMethods B. pinnatum flavonoids were characterized using FTIR and ultra‐high‐performance Liquid chromatography coupled with a mass spectrometry UPLC‐MS/MS. Thirty (30) male adult Wistar rats were used in this study and divided into five groups (n=6). Symptoms mimicking AD were induced in rats by administering 150mg/kg b.w of AlCl3 orally for 21 days. After the induction, animals were divided into five groups (n=6) and treated with BPF (50 and 100 mg/kg body weight) and 3 mg/kg of Rivastigmine for another 21 days. Neuro behavioral activities were assessed using Morris water maze tasks. Acetyl‐cholinesterase (AChE), BACE‐1 and oxidative stress markers were assessed following standard protocols. Semi‐quantitative reverse transcriptase‐PCR (RT‐PCR) was used to access the expression patterns of AChE and BACE‐1 mRNA in the cortex of rats.ResultsCharacterization of BPF revealed the presence of flavonols and flavone as the major constituents. Furthermore, AlCl3 overload caused behavioral alterations and showed impaired cognitive function similar to AD alongside increased brain cortical AChE activity, MDA level and decrease in antioxidant enzymes. In addition, AlCl3 induction caused the up‐regulation of AChE and BACE‐1 mRNA expressions in the cortex of rats. Conversely, oral administration of BPF (50 and 100 mg/kg body weight) significantly ameliorated cognitive deficits, restored oxidant‐antioxidant balance and modulated neurochemical markers, as evidenced by the improvement in brain function. Besides, BPF contributed towards the down‐regulation of AlCl3‐increased AChE and BACE‐1 mRNA expressions in the cortex.ConclusionThe current work demonstrates the therapeutic potential of B. pinnatum and suggests that it can ameliorate cognitive impairment caused by AlCl3 through reverting oxidative stress, restoring neurochemical function.

NECAB1 and NECAB2 are Prevalent Calcium-Binding Proteins of CB1/CCK-Positive GABAergic Interneurons.

The molecular repertoire of the “Ca2+-signaling toolkit” supports the specific kinetic requirements of Ca2+-dependent processes in different neuronal types. A well-known example is the unique expression pattern of calcium-binding proteins, such as parvalbumin, calbindin, and calretinin. These cytosolic Ca2+-buffers control presynaptic and somatodendritic processes in a cell-type-specific manner and have been used as neurochemical markers of GABAergic interneuron types for decades. Surprisingly, to date no typifying calcium-binding proteins have been found in CB1 cannabinoid receptor/cholecystokinin (CB1/CCK)-positive interneurons that represent a large population of GABAergic cells in cortical circuits. Because CB1/CCK-positive interneurons display disparate presynaptic and somatodendritic Ca2+-transients compared with other interneurons, we tested the hypothesis that they express alternative calcium-binding proteins. By in silico data mining in mouse single-cell RNA-seq databases, we identified high expression of Necab1 and Necab2 genes encoding N-terminal EF-hand calcium-binding proteins 1 and 2, respectively, in CB1/CCK-positive interneurons. Fluorescent in situ hybridization and immunostaining revealed cell-type-specific distribution of NECAB1 and NECAB2 throughout the isocortex, hippocampal formation, and basolateral amygdala complex. Combination of patch-clamp electrophysiology, confocal, and STORM super-resolution microscopy uncovered subcellular nanoscale differences indicating functional division of labor between the two calcium-binding proteins. These findings highlight NECAB1 and NECAB2 as predominant calcium-binding proteins in CB1/CCK-positive interneurons.

Spatial reference learning deficits in absence of dysfunctional working memory in the TgF344-AD rat model of Alzheimer's disease.

Alzheimer's disease (AD) is characterized by cognitive disorders and alterations of behavioral traits such as anhedonia and anxiety. Contribution of nonphysiological forms of amyloid and tau peptides to the onset of neurological dysfunctions remains unclear because most preclinical models only present one of those pathological AD-related biomarkers. A more recently developed model, the TgF344-AD rat has the advantage of overexpressing amyloid and naturally developing tauopathy, thus making it close to human familial forms of AD. We showed the presence of a learning dysfunction in a reference memory test, without spatial working memory impairment but with an increase in anxiety levels and a decrease in motivation to participate in the test. In the sucrose preference test, TgF344-AD rats did not show signs of anhedonia but did not increase the volume of liquid consumed when the water was replaced by sucrose solution. These behavioral phenomena were observed at an age when tau accumulation are absent, and where amyloid deposits are predominant in the hippocampus and the entorhinal cortex. Within the hippocampus itself, amyloid accumulation is heterogenous between the subiculum, the dorsal hippocampus and the ventral hippocampus. Thus, our data demonstrated heterogeneity in the appearance of various behavioral and neurochemical markers in the TgF344-AD rat. This multivariate analysis will therefore make it possible to define the stage of the pathology, to measure its evolution and the effects of future therapeutic treatments.

Myricitrinameliorates cognitive deficits in MCAOcerebral strokeratsvia histone acetylation-induced alterations of brain-derived neurotrophic factor.

The present study screened the effect of Myricitrin on cognitive deficits post-cerebral ischemic stroke and the involved mechanism. The rats were submitted to middle cerebral artery occlusion (MCAO) and were treated with sodium butyrate or Myricitrin (15 and 30mg/kg) for 28days. The spatial memory was studied by Morris water maze (MWM). After 4weeks, the rats were euthanized and hippocampus region was utilized for neurochemical and biochemical changes. The extent of histone acetylation was studied by ELISA. Protein levels were analyzed by Western blot analysis. The mRNA levels were analyzed by polymerase chain reaction (PCR). In silico bioinformatics docking studies were done for target confirmation of Myricitrin. The treatment of Myricitrin showed improved memory in MWM compared to rats treated with vehicle, and the effects of Myricitrin were similar to sodium butyrate-treated rats. At a dose of 30mg/kg Myricitrin, the histone deacetylase content was decreased, the expression levels of BDNF were increased, the levels of acetylated H3 and H4 along with Syn-I in the hippocampus region were over-expressed compared to control vehicle-treated rats. However, at low dose, i.e., 15mg/kg Myricitrin failed to show alterations in biochemical as well as neurochemical markers. Docking studies suggested the BDNF and Sun-I as potential target proteins of Myricitrin. The cognitive ameliorating effect of Myricitrin post-cerebral ischemia stroke can be attributed to increased expression of BDNF and Syn-I and modulation of histone acetylation.