Cortex Of Rats Research Articles

Upregulation of γ-synuclein in the prefrontal cortex and hippocampus following dopamine depletion: A study using the striatal 6-hydroxydopamine hemiparkinsonian rat model

Synucleins, including α-synuclein (α-syn), β-syn, and γ-syn, have been implicated in various synucleinopathies, notably Parkinson’s disease (PD), which has generated increased interest in understanding their roles. Although α-syn and β-syn have contrasting neuropathological consequences, the precise role of γ-syn remains unclear. This study validated non-motor symptoms, specifically anxiety-like behavior, along with the degradation of dopaminergic (DAergic) neurons in the nigrostriatal system and DAergic neurites in the prefrontal cortex and hippocampus of rats infused with striatal 6-hydroxydopamine (6-OHDA). Our study further investigated the alterations in γ-syn expression levels in the prefrontal cortices and hippocampi of these 6-OHDA–treated rats, aiming to establish foundational insights into the neuropathophysiology of DA depletion, a central feature of PD. Our findings revealed a significant increase in the expression of γ-syn mRNA and protein in these brain regions, in contrast to unaltered α- and β-syn expression levels. This suggests a distinct role of γ-syn within the neurobiological milieu under conditions of DA deficiency. Overall, our data shed light on the neurobiological changes observed in the hemiparkinsonian rat model induced with 6-OHDA, underscoring the potential significance of γ-syn in PD pathology.

Prenatal protein malnutrition decreases neuron numbers in the parahippocampal region but not prefrontal cortex in adult rats

ABSTRACT Objective Prenatal protein malnutrition produces anatomical and functional changes in the developing brain that persist despite immediate postnatal nutritional rehabilitation. Brain networks of prenatally malnourished animals show diminished activation of prefrontal areas and an increased activation of hippocampal regions during an attentional task [1]. While a reduction in cell number has been documented in hippocampal subfield CA1, nothing is known about changes in neuron numbers in the prefrontal or parahippocampal cortices. Methods In the present study, we used unbiased stereology to investigate the effect of prenatal protein malnutrition on the neuron numbers in the medial prefrontal cortex and the cortices of the parahippocampal region that comprise the larger functional network. Results Results show that prenatal protein malnutrition does not cause changes in the neuronal population in the medial prefrontal cortex of adult rats, indicating that the decrease in functional activation during attentional tasks is not due to a reduction in the number of neurons. Results also show that prenatal protein malnutrition is associated with a reduction in neuron numbers in specific parahippocampal subregions: the medial entorhinal cortex and presubiculum. Discussion The affected regions along with CA1 comprise a tightly interconnected circuit, suggesting that prenatal malnutrition confers a vulnerability to specific hippocampal circuits. These findings are consistent with the idea that prenatal protein malnutrition produces a reorganization of structural and functional networks, which may underlie observed alterations in attentional processes and capabilities.

Hierarchical gradients of multiple timescales in the mammalian forebrain.

Many anatomical and physiological features of cortical circuits, ranging from the biophysical properties of synapses to the connectivity patterns among different neuron types, exhibit consistent variation along the hierarchical axis from sensory to association areas. Notably, the scale of temporal correlation of neural activity at rest, known as the intrinsic timescale, increases systematically along this hierarchy in both primates and rodents, analogous to the growing scale and complexity of spatial receptive fields. However, how the timescales for task-related activity vary across brain regions and whether their hierarchical organization appears consistently across different mammalian species remain unexplored. Here, we show that both the intrinsic timescale and the timescales of task-related activity follow a similar hierarchical gradient in the cortices of monkeys, rats, and mice. We also found that these timescales covary similarly in both the cortex and basal ganglia, whereas the timescales of thalamic activity are shorter than cortical timescales and do not conform to the hierarchical order predicted by their cortical projections. These results suggest that the hierarchical gradient of cortical timescales might be a universal feature of intra-cortical circuits in the mammalian brain.

Maternal choline supplementation modulates cognition and induces anti-inflammatory signaling in the prefrontal cortices of adolescent rats exposed to maternal immune activation

Maternal infection has long been described as a risk factor for neurodevelopmental disorders, especially autism spectrum disorders (ASD) and schizophrenia. Although many pathogens do not cross the placenta and infect the developing fetus directly, the maternal immune response to them is sufficient to alter fetal neurodevelopment, a phenomenon termed maternal immune activation (MIA). Low maternal choline is also a risk factor for neurodevelopmental disorders, and most pregnant people do not receive enough of it. In addition to its role in neurodevelopment, choline is capable of inducing anti-inflammatory signaling through a nicotinic pathway. Therefore, it was hypothesized that maternal choline supplementation would blunt the neurodevelopmental impact of MIA in offspring through long-term instigation of cholinergic anti-inflammatory signaling.To model MIA in rats, the viral mimetic polyinosinic:polycytidylic acid (poly(I:C)) was used to elicit a maternal antiviral innate immune response in dams both with and without choline supplementation. Offspring were reared to both early and late adolescent stages (postnatal days 28 and 50, respectively), where anxiety-related behaviors and cognition were examined. After behavioral testing, animals were euthanized, and their prefrontal cortices (PFCs) were collected for analysis. MIA offspring demonstrated sex-specific patterns of altered cognition and repetitive behaviors, which were modulated by maternal choline supplementation. Choline supplementation also bolstered anti-inflammatory signaling in the PFCs of MIA animals at both early and late adolescent stages. These findings suggest that maternal choline supplementation may be sufficient to blunt some of the behavioral and neurobiological impacts of inflammatory exposures in utero, indicating that it may be a cheap, safe, and effective intervention for neurodevelopmental disorders.

Features of reactions to stress in rats with passive-defense behavior after light desynchronosis and physical activity

An assessment was made of hematological parameters of peripheral blood and structural and functional changes in the adrenal glands in stress-unresistant rats (passive-defensive type of behavior in the open field test) after exposure to light deprivation and physical activity during the spring equinox. The experiment showed that light deprivation for 10 days reduces the total number of leukocytes, the absolute content of monocytes, granulocytes, lymphocytes and the level of corticosterone in the peripheral blood compared to the intact group, that was on a natural lighting regime. Histological analysis of the adrenal glands of this group showed, that in the zona fasciculata under such conditions there was nuclear hypertrophy, an increase in the nuclear-cytoplasmic ratio of adrenocorticocytes and a decrease in the size of the zona glomerulosa of the adrenal cortex of rats in relation to the intact group. Physical activity in the form of forced swimming until complete fatigue for 5 days in a row in natural light in stress-unresistant rats did not change the parameters of the peripheral blood of animals, however it led to an increase in the area of the cytoplasm, the nuclear-cytoplasmic ratio, as well as the formation of hypertrophy of the nuclei of adrenocorticocytes in the fascicle adrenal zones, which indicated the preparation of cells for increased synthetic activity. Keeping rats for 10 days in complete darkness before forced swimming every day for 5 days, on the one hand, formed a hypoxic state and exhaustion of the adrenal glands, on the other hand, stabilized the leukocyte pool of peripheral blood compared to similar indicators in intact rats.

Recording of single-unit activities with flexible micro-electrocorticographic array in rats for decoding of whole-body navigation

Objective.Micro-electrocorticographic (μECoG) arrays are able to record neural activities from the cortical surface, without the need to penetrate the brain parenchyma. Owing in part to small electrode sizes, previous studies have demonstrated that single-unit spikes could be detected from the cortical surface, and likely from Layer I neurons of the neocortex. Here we tested the ability to useμECoG arrays to decode, in rats, body position during open field navigation, through isolated single-unit activities.Approach. μECoG arrays were chronically implanted onto primary motor cortex (M1) of Wistar rats, and neural recording was performed in awake, behaving rats in an open-field enclosure. The signals were band-pass filtered between 300-3000 Hz. Threshold-crossing spikes were identified and sorted into distinct units based on defined criteria including waveform morphology and refractory period. Body positions were derived from video recordings. We used gradient-boosting machine to predict body position based on previous 100 ms of spike data, and correlation analyses to elucidate the relationship between position and spike patterns.Main results.Single-unit spikes could be extracted during chronic recording fromμECoG, and spatial position could be decoded from these spikes with a mean absolute error of prediction of 0.135 and 0.090 in the x- and y- dimensions (of a normalized range from 0 to 1), and Pearson's r of 0.607 and 0.571, respectively.Significance. μECoG can detect single-unit activities that likely arise from superficial neurons in the cortex and is a promising alternative to intracortical arrays, with the added benefit of scalability to cover large cortical surface with minimal incremental risks. More studies should be performed in human related to its use as brain-machine interface.

ISRIB ameliorates spatial learning and memory impairment induced by adolescent intermittent ethanol exposure in adult male rats

Alcohol exposure in adolescence is considered a major cause of cognitive impairments later in life including spatial learning and memory. Integrated stress response (ISR), a program of conservative translation and transcription, is crucial in synaptic plasticity and memory. Although previous studies have elucidated ISR in different brain areas involved in learning and memory disorders, the impact of ISR on learning and memory following adolescent alcohol exposure remains unclear. Here, we demonstrated that adolescent intermittent ethanol (AIE) exposure caused spatial learning and memory impairment, combined with neuronal damage in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc) and hippocampus (HIP) in adult rats. Moreover, integrated stress response inhibitor (ISRIB) administration not only improved spatial learning and memory impairment and neuronal damage but also inhibited the endoplasmic reticulum stress (ER) and reversed changes in synaptic proteins. These findings suggested that ISRIB ameliorates AIE exposure-induced spatial learning and memory deficits by improving neural morphology and synaptic function through inhibiting ER stress signaling pathway in the mPFC, NAc and HIP in adulthood. Our findings may enhance comprehension of cognitive function and neuronal effects of adolescent ethanol exposure and ISRIB treatment may be an underlying potential option for addressing alcohol-induced learning and memory deficits.

Neuroprotective effect of long-term resistance physical exercise against memory damage elicited by a lipopolysaccharide-induced neuroinflammation model in malerats.

Resistance exercise training (RET) is considered an excellent tool for preventing diseases with an inflammatory background. Its neuroprotective, antioxidant, and anti-inflammatory properties are responsible for positively modulating cholinergic and oxidative systems, promoting neurogenesis, and improving memory. However, the mechanisms behind these actions are largely unknown. In order to investigate the pathways related to these effects of exercise, we conducted a 12-week long-term exercise training protocol and used lipopolysaccharide (LPS) to induce damage to the cortex and hippocampus of male Wistar rats. The cholinergic system, oxidative stress, and histochemical parameters were analyzed in the cerebral cortex and hippocampus, and memory tests were also performed. It was observed that LPS: (1) caused memory loss in the novel object recognition (NOR) test; (2) increased the activity of acetylcholinesterase (AChE) and Iba1 protein density; (3) reduced the protein density of brain-derived neurotrophic factor (BDNF) and muscarinic acetylcholine receptor M1 (CHRM1); (4) elevated the levels of lipid peroxidation (TBARS) and reactive species (RS); and (5) caused inflammatory damage to the dentate gyrus. RET, on the other hand, was able to prevent all alterations induced by LPS, as well as increase per se the protein density of the alpha-7 nicotinic acetylcholine receptor (nAChRα7) and Nestin, and the levels of protein thiols (T-SH). Overall, our study elucidates some mechanisms that support resistance physical exercise as a valuable approach against LPS-induced neuroinflammation and memory loss.

Effects of Schisandrae Chinensis Fructus Lignans on Alertness of Rats With Sleep Deprived by Treadmill Exercise

Objective To investigate the effects of Schisandrae Chinensis Fructus lignans on the alertness of the rats with sleep deprived by treadmill exercise and the underlying neurobiological mechanism. Methods According to the random number table method,SD male rats were assigned into control,sleep deprivation,low-,medium-,and high-dose Schisandrae Chinensis Fructus lignans,and atomoxetine hydrochloride groups,with 8 rats in each group.The rats in other groups except the control group were subjected to sleep deprivation by treadmill exercise for 3 d.During the deprivation period,each administration group was administrated with the corresponding drug by gavage,and a 5-9 hole tester was used to test the alertness performance of rats in each group. Furthermore,other SD male rats were selected and randomized into control,sleep deprivation,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride groups,with 10 rats in each group.The rats were modeled with the sleep deprivation method the same as that above and administrated with corresponding agents.ELISA was employed to measure the serum level of orexin A in each group of rats.The protein levels of c-Fos,orexin receptor 1,and orexin receptor 2 in the prefrontal cortex of rats in each group were observed by immunofluorescence and Western blotting. Results Compared with the control group,sleep deprivation reduced the choice accuracy (P<0.001) and increased the omission responses,omission percent,and mean correct response latency (P=0.002,P=0.003,P=0.020).Compared with the sleep deprivation group,medium- and high-dose Schisandrae Chinensis Fructus lignans and atomoxetine hydrochloride improved the alertness of rats,as demonstrated by the increased choice accuracy (P=0.001,P=0.006,P<0.001) and reduced omission responses (P=0.001,P=0.001,P<0.001),omission percent (P=0.001,P=0.002,P<0.001),and mean correct response latency (P=0.018,P=0.003,P=0.014).Compared with the control group,the sleep deprivation group showed elevated level of orexin A in the serum (P<0.001),up-regulated expression of c-Fos (P<0.001),and down-regulated expression of orexin receptor 1 (P=0.037) in the prefrontal cortex.Compared with the sleep deprivation group,Schisandrae Chinensis Fructus lignans (67.2 mg/kg) and atomoxetine hydrochloride lowered the orexin A level in the serum (P=0.005,P=0.029),down-regulated the expression of c-Fos (P=0.028,P=0.036),and up-regulated the expression of orexin receptor 1 (P=0.043,P=0.013) in the prefrontal cortex. Conclusion Schisandrae Chinensis Fructus lignans may antagonize the alertness decrease caused by sleep deprivation by regulating the secretion of orexin and the expression of orexin receptor 1 in the prefrontal cortex.

Caffeine alleviate lipopolysaccharide-induced neuroinflammation and depression through regulating p-AKT and NF-κB

Caffeine, a nonselective adenosine receptor antagonist, is the major component of coffee and the most consumed psychostimulant at nontoxic doses in the world. It has been identified that caffeine consumption reduces the risk of several neurological diseases. However, the mechanisms by which it impacts the pathophysiology of neurological diseases remain to be elucidated. In this study, we investigated whether caffeine exerts anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation and depression in vivo and explored the potential mechanism of caffeine through LPS-induced brain injury. Adult male Sprague-Dawley (SD) rats were intraperitoneal injected with various concentrations of LPS to induce the neuroinflammation and depressive-like behavior. Then SD rats were treated with caffeine in the presence or absence of LPS. Open-filed and closed-field tests were applied to detect the behaviors of SD rats, while western blot was performed to measure the phosphorylation level of protein kinase B (p-AKT) and nuclear factor κB (NF-κB) in the cortex after caffeine was orally administered. Our findings indicated that caffeine markedly improved the neuroinflammation and depressive-like behavior of LPS-treated SD rats. Mechanistic investigations demonstrated that caffeine down-regulated the expression of p-AKT and NF-κB in LPS-induced SD rats cortex. Taken together, these results indicated that caffeine, a potential agent for preventing inflammatory diseases, may suppress LPS-induced inflammatory and depressive responses by regulating AKT phosphorylation and NF-κB.

Host circuit engagement of human cortical organoids transplanted in rodents.

Human neural organoids represent promising models for studying neural function; however, organoids grown in vitro lack certain microenvironments and sensory inputs that are thought to be essential for maturation. The transplantation of patient-derived neural organoids into animal hosts helps overcome some of these limitations and offers an approach for neural organoid maturation and circuit integration. Here, we describe a method for transplanting human stem cell-derived cortical organoids (hCOs) into the somatosensory cortex of newborn rats. The differentiation of human induced pluripotent stem cells into hCOs occurs over 30-60 days, and the transplantation procedure itself requires ~0.5-1 hours per animal. The use of neonatal hosts provides a developmentally appropriate stage for circuit integration and allows the generation and experimental manipulation of a unit of human neural tissue within the cortex of a living animal host. After transplantation, animals can be maintained for hundreds of days, and transplanted hCO growth can be monitored by using brain magnetic resonance imaging. We describe the assessment of human neural circuit function in vivo by monitoring genetically encoded calcium responses and extracellular activity. To demonstrate human neuron-host functional integration, we also describe a procedure for engaging host neural circuits and for modulating animal behavior by using an optogenetic behavioral training paradigm. The transplanted human neurons can then undergo ex vivo characterization across modalities including dendritic morphology reconstruction, single-nucleus transcriptomics, optogenetic manipulation and electrophysiology. This approach may enable the discovery of cellular phenotypes from patient-derived cells and uncover mechanisms that contribute to human brain evolution from previously inaccessible developmental stages.

Effect of curcumin-donepezil combination on spatial memory, astrocyte activation, and cholinesterase expressions in brain of scopolamine-treated rats.

The study investigated the effect of co-administration of curcumin and donepezil on several markers of cognitive function (such as spatial memory, astrocyte activation, cholinesterase expressions) in the brain cortex and hippocampus of scopolamine-treated rats. For seven consecutive days, a pre-treatment of curcumin (50mg/kg) and/or donepezil (2.5mg/kg) was administered. On the seventh day, scopolamine (1mg/kg) was administered to elicit cognitive impairment, 30min before memory test was conducted. This was followed by evaluating changes in spatial memory, cholinesterase, and adenosine deaminase (ADA) activities, as well as nitric oxide (NO) level were determined. Additionally, RT-qPCR for glial fibrillary acidic protein (GFAP) and cholinesterase gene expressions was performed in the brain cortex and hippocampus. Also, GFAP immunohistochemistry of the brain tissues for neuronal injury were performed in the brain cortex and hippocampus. In comparison to the control group, rats given scopolamine had impaired memory, higher levels of acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and ADA activities, as well as elevated markers of oxidative stress. In addition to enhanced GFAP immunoreactivity, there was also overexpression of the GFAP and BChE genes in the brain tissues. The combination of curcumin and donepezil was, however, observed tobetter ameliorate these impairments in comparison to thedonepezil-administered rat group. Hence, this evidence provides more mechanisms to support the hypothesis that the concurrent administration of curcumin and donepezil mitigates markers of cognitive dysfunction in scopolamine-treated rat model.

Effects of adolescent intermittent ethanol exposure on cortical perineuronal net and parvalbumin expression in adulthood mediate behavioral inflexibility.

Alcohol is commonly consumed by adolescents in a binge-like pattern, which can lead to long-lasting cognitive deficits, including reduced behavioral flexibility. We and others have determined that adolescent intermittent ethanol (AIE) exposure leads toincreased number of perineuronal net (PNN) numbers in brain regions that are important for behavioral flexibility. However, whether altered neurochemistry stemming from AIE exposure plays a significant role in reduced behavioral flexibility is unknown. We measured the number and size of parvalbumin expressing (PV+) interneurons and associated PNNs within the orbitofrontal cortex (OFC), prelimbic cortex (PrL), infralimbic cortex (IL), and anterior insular cortex (AIC) of female and male rats following AIE or control exposure and subsequent training on an attentional set-shift task (ASST). We then ran analyses to determine whether AIE-induced changes in PV and PNN measures statistically mediated the AIE-induced behavioral deficit in reversal learning. We demonstrate that AIE exposure impaired behavioral flexibility on reversal two of the ASST (i.e., recalling the initial learned associations), and led to smaller PV+ cells and increased PNN numbers in the AIC. Interestingly, PNN size and number were not altered in the PrL or IL following AIE exposure, in contrast to prior reports. Mediation analyses suggest that AIE alters behavioral flexibility, at least in part through changes in PV and PNN fluorescent measures in the AIC. This study reveals a significant link between AIE exposure, neural alterations, and diminished behavioral flexibility in rats, and highlights a potential novel mechanism comprising changes in PV and PNN measures within the AIC. Future studies should explore the impact of PNN degradation within the AIC on behavioral flexibility.

Increased Prorenin Expression in the Kidneys May Be Involved in the Abnormal Renal Function Caused by Prolonged Environmental Exposure to Microcystin-LR.

Toxic algae in eutrophic lakes produce cyanotoxic microcystins. Prior research on the effect of microcystin-LR in the kidney utilized intraperitoneal injections, which did not reflect natural exposure. Oral microcystin-LR research has focused on renal function and histopathology without examining the molecular mechanisms. The present study aimed to evaluate the mechanism of microcystin-LR in the kidneys via oral administration in WKAH/HkmSlc rats over 7 weeks, alongside stimulation of the proximal tubular cells. Although there were no differences in the concentrations of plasma albumin, blood urea nitrogen, and creatinine, which are parameters of renal function, between the control and microcystin-LR-administrated rats, prorenin expression was significantly increased in the renal cortex of the rats administered microcystin-LR and the microcystin-LR-treated proximal tubular cells. The expression levels of (pro)renin receptor (PRR), transforming growth factor-β1 (TGFβ1), and α-smooth muscle actin (α-SMA) in the renal cortex did not differ significantly between the control and microcystin-LR-administered rats. However, the expression levels of prorenin were significantly positively correlated with those of PRR, TGFβ1, and α-SMA in the renal cortex of rats administered microcystin-LR. Additionally, a significant positive correlation was observed between the expression levels of TGFβ1 and α-SMA. Collectively, increased prorenin expression caused by the long-term consumption of microcystin-LR may initiate a process that influences renal fibrosis and abnormal renal function by regulating the expression levels of PRR, TGFβ1, and α-SMA.

“Blocking-like” effects in attentional set-shifting: Redundant cues facilitate shifting in male rats with medial prefrontal cortex inactivation

Without a functioning prefrontal cortex, humans and other animals are impaired in measures of cognitive control and behavioral flexibility, including attentional set-shifting. However, the reason for this is unclear with evidence suggesting both impaired and enhanced attentional shifting. We inhibited the medial prefrontal cortex (mPFC) of rats while they performed a modified version of an attentional set-shifting task to explore the nature of this apparent contradiction.Twelve adult male Lister hooded rats received AAV5-CaMKIIa-hM4D(Gi)-mCherry viral vector bilaterally into mPFC to express inhibitory ‘Designer Receptors Exclusively Activated by Designer Drugs’ (iDREADDs). The receptors were activated by systemic clozapine N-oxide (CNO) to inhibit mPFC function. The rats were tested in the standard attentional set-shifting task four times: twice after i.p. administration and twice after oral administration of vehicle or CNO (10 mg/kg). They were then tested twice in a modified task, with or without oral CNO. The modified task had an extra stage before the extradimensional shift, in which the relevant exemplars remained relevant and new exemplars that were fully predictive but redundant replaced the previous irrelevant exemplars. These exemplars then became relevant at the subsequent ED stage.In the standard task, mPFC inactivation impaired attentional set-shifting, consistent with previous findings. However, in the modified task, mPFC inactivation abolished ED shift-costs. The results support the suggestion that the mPFC is needed for the downregulation of attention that prevents learning about redundant and irrelevant stimuli. With mPFC inactivated, the rat learns more rapidly when previously redundant exemplars become the only relevant information.

Single-Trial Representations of Decision-Related Variables by Decomposed Frontal Corticostriatal Ensemble Activity.

The frontal cortex-striatum circuit plays a pivotal role in adaptive goal-directed behaviors. However, it remains unclear how decision-related signals are mediated through cross-regional transmission between the medial frontal cortex and the striatum by neuronal ensembles in making decision based on outcomes of past action. Here, we analyzed neuronal ensemble activity obtained through simultaneous multiunit recordings in the secondary motor cortex (M2) and dorsal striatum (DS) in rats performing an outcome-based left-or-right choice task. By adopting tensor component analysis (TCA), a single-trial-based unsupervised dimensionality reduction approach, for concatenated ensembles of M2 and DS neurons, we identified distinct three spatiotemporal neural dynamics (TCA components) at the single-trial level specific to task-relevant variables. Choice-position-selective neural dynamics reflected the positions chosen and was correlated with the trial-to-trial fluctuation of behavioral variables. Intriguingly, choice-pattern-selective neural dynamics distinguished whether the incoming choice was a repetition or a switch from the previous choice before a response choice. Other neural dynamics was selective to outcome and increased within-trial activity following response. Our results demonstrate how the concatenated ensembles of M2 and DS process distinct features of decision-related signals at various points in time. Thereby, the M2 and DS collaboratively monitor action outcomes and determine the subsequent choice, whether to repeat or switch, for action selection.

Moderate aerobic training counterbalances the deleterious effect of undernutrition on oxidative balance and mitochondrial markers

The state of Maternal Protein Malnutrition (MPM) is associated with several deleterious effects, including inflammatory processes and dysregulation in oxidative balance, which can promote neurodegeneration. On the other hand, it is known that aerobic exercise can promote systemic health benefits, combating numerous chronic diseases. Therefore, we evaluate the effect of aerobic exercise training (AET) on indicators of mitochondrial bioenergetics, oxidative balance, endoplasmic reticulum stress, and neurotrophic factor in the prefrontal cortex of malnourished juvenile Wistar rats. Pregnant Wistar rats were fed with a diet containing 17% or 8% casein during pregnancy and lactation. At 30 days of life, male offspring were divided into 4 groups: Low-Protein Control (LS), Low-Protein Trained (LT), Normoprotein Control (NS), and Normoprotein Trained (NT). The trained groups performed an AET for 4 weeks, 5 days a week, 1 h a day per session. At 60 days of life, the animals were sacrificed and the skeletal muscle, and prefrontal cortex (PFC) were removed to evaluate the oxidative metabolism markers and gene expression of ATF-6, GRP78, PERK and BDNF. Our results showed that MPM impairs oxidative metabolism associated with higher oxidative and reticulum stress. However, AET restored the levels of indicators of mitochondrial bioenergetics, in addition to promoting resilience to cellular stress. AET at moderate intensity for 4 weeks in young Wistar rats can act as a non-pharmacological intervention in fighting against the deleterious effects of a protein-restricted maternal diet.

Effects of early monocular enucleation on cortical spreading depression in well-nourished and malnourished adult rats.

Sensory development is a complex process that can influence physiological and pathological factors. In laterally-eyed mammals, monocular enucleation (ME) during development and the subsequent lack of external sensory stimuli can result in permanent morphological and physiological changes. Malnutrition, especially in early life, also can cause permanent morphofunctional changes due to inadequate nutrient intake in both hemispheres. This study investigated the effects of early (postnatal day 7) ME and malnutrition during the suckling period on cortical excitability in adulthood (110-140 days of life). For this, we compared the speed propagation of cortical spreading depression in the occipital and parietal cortex of malnourished and well-nourished adult rats, previously suckled small-sized litters with three pups (L3/dam) medium-sized litters with six pups (L6/dam), and large-sized litters with twelve pups (L12/dam). The CSD velocity was augmented by the ME in the contralateral side of the removed eye in the parietal and occipital cortex. These findings suggest that visual sensory input deprivation is associated with permanent functional changes in the visual pathways, which can alter cortical excitability and lead to modifications in CSD propagation.

Identification of differentially expressed genes in the medial prefrontal cortex of rats subjected to chronic unpredictable mild stress and treated with electroacupuncture

Major depressive disorder is a chronic mental health condition that seriously impacts afflicted individuals. Although electroacupuncture has proven to be an effective therapy for depression, its underlying biological mechanism remains largely unknown. In this study, we aimed to investigate the effects of electroacupuncture on depression-like behavior and to identify potential target genes related to those effects. To achieve this, we subjected rats to chronic unpredictable mild stress (CUMS) and used sucrose preference, forced swimming, and open-field tests to determine their depression-like behavior in the absence or after receipt of electroacupuncture treatment. RNA sequencing technology was then used to reveal the differentially expressed genes associated with depression and electroacupuncture treatment effects in the medial prefrontal cortex (mPFC). Repeated electroacupuncture treatments at the Baihui (GV20) and Taichong (LR3) acupoints significantly alleviated depression-like behavioral defects in the animals. Genomic RNA sequencing revealed several significant changes in the mPFC transcriptome of rats that received treatment. Through differential gene expression analysis, we found that electroacupuncture reversed the CUMS-induced downregulation of 46 genes and upregulation of 13 genes. Among the differentially expressed genes, Casr, Bdkrb2, Gnb3, and Ccl1 were found to be associated with depression and electroacupuncture treatment effects. In conclusion, we verified that electroacupuncture treatment has an effective antidepressant effect, and the underlying mechanism involves multiple systems and targets.

Reduced ischemia‐reperfusion oxidative stress injury by melatonin and N‐acetylcysteine in the male rat brain

Middle cerebral artery occlusion (MCAO) is a model for inducing ischemic stroke in rodents, leading to devastating brain damage. Oxidative stress (OS) plays a crucial role in the pathogenesis of ischemia. In this study, the effect of melatonin and N-acetylcysteine on ischemia-reperfusion-induced oxidative stress injury in the cerebral cortex of male rats was investigated. 30 male Wistar rats were divided into sham, ischemic, NAC, melatonin and NAC + melatonin groups. All groups, except the sham group, underwent MCAO on the left side, and the treatment groups received intraperitoneal injections of either 50 mg/kg N-acetylcysteine (NAC) or 5 mg/kg melatonin or a combination of both 24 and 48 hours later. At 24 and 72 hours after surgery, the animals were examined for sensory and motor activity. The cerebral cortex was dissected after sacrificing the rats, infarct volume estimated and the concentrations of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and nuclear factor erythroid-2 related factor 2 (Nrf2) were analyzed by enzyme-linked immunosorbent assay (ELISA). The results indicate that the NAC + melatonin group exhibited elevated sensory-motor activity and a reduced infarct volume rate in comparison to the ischemic group (p≤ 0.05). Compared to the ischemic group, the NAC + melatonin group showed a significant increase in SOD concentration and a significant decrease in MDA (p≤ 0.05). It can therefore be concluded that the simultaneous administration of NAC and melatonin can reduce the cerebral infarction volume, and improve neurological functions by modulating SOD and MDA.