Neuromorphological Changes Research Articles

The Lack of TRPA1 Ion Channel Does Not Affect the Chronic Stress-Induced Activation of the Locus Ceruleus.

We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger-Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control. We aimed at investigating whether the TRPA1 is expressed in the LC, and to test if the response to chronic variable mild stress (CVMS) is affected by a lack of TRPA1. The TRPA1 expression was examined via RNAscope in situ hybridization. We investigated TRPA1 knockout and wildtype mice using the CVMS model of depression. Tyrosine hydroxylase (TH) and FOSB double immunofluorescence were used to test the functional neuromorphological changes in the LC. No TRPA1 expression was detected in the LC. The TH content was not affected by CVMS exposure. The CVMS-induced FOSB immunosignal did not co-localize with the TH neurons. TRPA1 is not expressed in the LC. A lack of functional TRPA1 receptor neither directly nor indirectly affects the TH content of LC neurons under CVMS.

The antipsychotic olanzapine reduces memory deficits and neuronal abnormalities in a male rat model of Autism

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental condition that impacts social interaction and sensory processing, is rising. Valproic acid (VPA) exposure during pregnancy causes autistic-like traits in offspring. Olanzapine (OLZ), an atypical antipsychotic, is used to treat ASD. We assessed the impact of OLZ on behavior, neuromorphology, and nitric oxide (NO) levels in the hippocampus using prenatal VPA treatment in rats. It is commonly known that ASD patients exhibit sensory abnormalities. As such, we utilized the tail flick test to validate the ASD model. In the novel object recognition test (NORT), VPA exposure reduces the discrimination index (DI) in the first introduction to the novel object. Moreover, OLZ and vehicle-treated rats perform differently in the second exposition to the DI of the novel object, suggesting that OLZ reverses VPA-induced deficits in recognition memory. The latency to find the hidden platform in the Morris water maze test of memory and learning improves in VPA-exposed rats after OLZ administration, indicating that OLZ improves spatial memory in these rats. Administration of prenatal VPA induces neuronal hypotrophy and reduces spine density in pyramidal neurons of the CA1 region of the hippocampus. Treatment with OLZ corrects the neuromorphological changes brought on by VPA. In the CA1 region of the hippocampus, VPA treatment increases the number of neurons, which normalizes with OLZ treatment. OLZ increases the NO levels in the dorsal hippocampus in control rats. In rats exposed to VPA, the second-generation antipsychotic OLZ reduces memory-related and neuroplastic alterations. The current findings support the use of OLZ in this illness and further validate the use of prenatal VPA as a model of ASD.

Upregulation of Microglial Sirt6 and Inhibition of Microglial Activation by Vitamin D3 in Lipopolysaccharide-stimulated Mice and BV-2 Cells

Vitamin D3 may suppress microglial activation and neuroinflammation, which play a central role in the pathophysiology of many neurological disorders. Sirt6 can remove histone 3 lysine 9 acetylation (H3K9ac) to repress expression of pathological genes and produce anti-inflammatory effects. However, whether vitamin D3 upregulates microglial Sirt6 to exert its protective effects against microglial activation and neuroinflammation is unclear. The effects of lower, normal, and higher dosages (1, 10 and 100 μg/kg/day) of vitamin D3 on behavioral and neuromorphological changes, brain inflammatory factors, Sirt6 and H3K9ac levels, and microglial Sirt6 distribution in hippocampus were evaluated in lipopolysaccharide (LPS)-stimulated mice. In addition, the effects of vitamin D3 on inflammatory factors, reactive oxygen species, Sirt6, and H3K9ac were confirmed in LPS-stimulated BV-2 cells. We verified that vitamin D3 ameliorated the impaired sociability of LPS-stimulated mice by three-chamber test. In addition, vitamin D3 upregulated brain Sirt6 generation, reduced H3K9ac levels and inhibited generation of brain inflammatory factors. Moreover, vitamin D3 promoted microglial Sirt6 distribution and attenuated microglia displaying an activated morphology in the hippocampus of LPS-stimulated mice. Similarly, vitamin D3 upregulated Sirt6 generation and intensity, reduced H3K9ac levels, and inhibited the inflammatory activation of LPS-stimulated BV-2 cells. In conclusion, vitamin D3 may upregulate microglial Sirt6 to reduce H3K9ac and inhibit microglial activation, thereby antagonizing neuroinflammation.

МЕЖДИСЦИПЛИНАРНЫЕ ПОДХОДЫ К ОЦЕНКЕ ЦЕРЕБРАЛЬНЫХ ИЗМЕНЕНИЙ ПРИ РАДИАЦИОННЫХ ВОЗДЕЙСТВИЯХ

When exposed to even a small dose of an ionizing phenomenon, a significant increase in neuropsychiatric diseases is observed in the future, which were difficult to succumb to and persisted throughout the life span. Despite the fact that in most cases there is a dysfunction of a borderline nature, they are manifested by cognitive disorders, decreased performance and early aging of the body. High medical and social sensitivity to such problems is detected, the relevance of identifying neuromorphological changes in the central nervous system is determined. However, the observed neuromorphological and statistical methods do not make it possible to reveal the probability of the occurrence of radiation damage to the brain and to assess the role of the ionizing factor in the growth of morbidity is rather laborious. It is clear that interdisciplinary approaches are needed to assess radiation-induced changes in the brain in experimental experimental and mathematical modeling.

Neuromorphological and behavioural effects of early developmental exposure to alarm cue on captive-reared Atlantic salmon (Salmo salar)

Behavioural plasticity plays an important role in an organism's ability to adapt to captive settings, but a lack of perceived predation risk during early development in captivity can lead to diminished anti-predator behaviours. Here, we used Atlantic salmon ( Salmo salar) to test whether early developmental exposure to alarm cues (pre-exposure) led to (1) a developmentally plastic response to alarm cue in yearling and (2) an observable change in neural investment. We exposed fry to either a conspecific alarm cue (pre-exposed fish) or control water (non-exposed fish) and measured activity related to anti-predator behaviour such as time spent motionless, number of aggressive acts, and time spent associated with shelter. We found no indication of a developmentally plastic response to early alarm cue exposure, but we found that pre-exposed fish developed relatively smaller olfactory bulbs compared to non-exposed fish. Our results demonstrate the importance of and ability to exploit plastic responses in captive-reared Atlantic salmon and highlight the need to link behaviour with neuromorphological changes.

Artificial Intelligence Analysis of Nerve Fibers Based on Corneal Confocal Microscopy

Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. Traditional DPN diagnostic methods are based on clinical symptoms and signs as well as electrophysiological examination, which are mainly used to detect the lesions of large nerve fibers. However, the small nerve fibers are the earliest ones damaged in DPN. Corneal confocal microscopy (CCM) can analyze the changes of corneal nerve fibers under a high power microscope. It is a rapid, repeatable and quantitative noninvasive technique to measure small nerve fibers. It can diagnose DPN early and evaluate neuromorphological changes prospectively. It has a good application expectation. During this article, we summarized the role and limitations of DPN's most reliable parameters of corneal nerve in evaluating diabetic autonomic neuropathy and diabetic micro-vascular complications. Further, we reviewed the clinical application of CCM in evaluating diabetic neuropathy and analysis methods of CCM related artificial intelligence, in order to provide references for clinical diagnosis and treatment.

Neuromorphology of cognitive changes in type 2 diabetes mellitus

According to the WHO today about 422 million people worldwide have diabetes and chronic course of diabetes leads over time to decrease the cognitive functions and the development of dementia. The aim of this study was to decipher neuromorphological changes in type 2 diabetes that potentially affect cognitive impairment.

Neuromorphological Changes following Selection for Tameness and Aggression in the Russian Farm-Fox experiment.

The Russian farm-fox experiment is an unusually long-running and well-controlled study designed to replicate wolf-to-dog domestication. As such, it offers an unprecedented window onto the neural mechanisms governing the evolution of behavior. Here we report evolved changes to gray matter morphology resulting from selection for tameness versus aggressive responses toward humans in a sample of 30 male fox brains. Contrasting with standing ideas on the effects of domestication on brain size, tame foxes did not show reduced brain volume. Rather, gray matter volume in both the tame and aggressive strains was increased relative to conventional farm foxes bred without deliberate selection on behavior. Furthermore, tame- and aggressive-enlarged regions overlapped substantially, including portions of motor, somatosensory, and prefrontal cortex, amygdala, hippocampus, and cerebellum. We also observed differential morphologic covariation across distributed gray matter networks. In one prefrontal-cerebellum network, this covariation differentiated the three populations along the tame-aggressive behavioral axis. Surprisingly, a prefrontal-hypothalamic network differentiated the tame and aggressive foxes together from the conventional strain. These findings indicate that selection for opposite behaviors can influence brain morphology in a similar way.SIGNIFICANCE STATEMENT Domestication represents one of the largest and most rapid evolutionary shifts of life on earth. However, its neural correlates are largely unknown. Here we report the neuroanatomical consequences of selective breeding for tameness or aggression in the seminal Russian farm-fox experiment. Compared with a population of conventional farm-bred control foxes, tame foxes show neuroanatomical changes in the PFC and hypothalamus, paralleling wolf-to-dog shifts. Surprisingly, though, aggressive foxes also show similar changes. Moreover, both strains show increased gray matter volume relative to controls. These results indicate that similar brain adaptations can result from selection for opposite behavior, that existing ideas of brain changes in domestication may need revision, and that significant neuroanatomical change can evolve very quickly, within the span of <100 generations.

Social isolation-induced effects on male-specific courtship behaviours and dendritic architecture in associative forebrain areas in Zebra finches (Taeniopygia guttata)

Zebra finches ( Taeniopygia guttata) are highly monogamous birds that maintain lifelong pair-bonds. Females make the mate choice based on the quality of males who initiate pair-bond formation by courting the female. A mate separation-reunion paradigm can help to evaluate the adaptive value of social affiliation of male finches and their affinity to new females in absence of mated females which can manifest at a neuronal level by dendritic measures. The aim of this study was to examine behavioural and neuronal changes as a result of social isolation following pair-bonding in male zebra finches. Towards this, male zebra finches from a pair-bonded group were isolated for a period of ten days and then exposed to either the mate or a new female. Four main courtship behaviours: clumping, allopreening, nest box occupancy and directed singing were recorded and analysed. Brains were processed by a modified Golgi technique to detect changes in dendritic arborizations using the Sholl analysis. Baseline behavioural results showed an increase in clumping and nest box activity by day 10. Isolated males re-introduced with their pair-bonded females demonstrated increased nest box activity. Alternatively, isolated males exposed to new females demonstrated increased directed singing when compared to their pair-bonded state, but lower than when exposed to same female. Neuro-morphological changes assessed through quantification of dendritic intersections and branch points were observed in pallial brain areas known to be implicated in the development of social/sexual preferences, with the pair-bonded group demonstrating more branching and longer dendrites when compared to the socially-isolated group. Thus social isolation impacts both courtship behaviour and neuronal morphologies with differential responses to the pair-bonded female versus a new female.

Cortical gyrification morphology in PTSD: A neurobiological risk factor for severity?

Post-traumatic stress disorder (PTSD) is a prevalent psychiatric disorder, particularly among military personnel and veterans. Cortical gyrification, as a specific metric derived from structural MRI, is an index of the convoluted folding and patterning of the gyri and sulci, and is thought to facilitate the efficiency of local neuronal wiring. It has the potential to act as a neurobiological risk factor for emergent psychiatric disorders – to date, it has been understudied in PTSD. Here, using a local measure of the degree of gyrification (local Gyrification Index, lGI) we investigate cortical gyrification morphology in 48 adult male soldiers with (n = 23) and without (n = 25) a PTSD diagnosis. We also examine the relation between lGI and PTSD severity within the PTSD group. General linear models yielded significant between-group differences with greater lGI found in PTSD in a cluster located in the medial occipito-parietal lobe on the left hemisphere and reduced lGI in a cluster located on the lateral surface of the parietal lobe on the right hemisphere. Brain-behaviour analyses within the PTSD group yielded significant positive associations between lGI and PTSD severity in a cluster located in the frontal cortex of the left hemisphere and scattered clusters located within all lobes of the right hemisphere. After accounting for the effects of comorbid psychiatric symptoms common in PTSD, the associations in the right hemisphere reduced to clusters only located in the frontal lobe, while the cluster in the left hemisphere remained significant. Our results suggest that atypical cortical gyrification in parietal and occipital regions may be implicated in the psychopathology of PTSD diagnosis, and properties of prefrontal gyrification associated with the emergent severity of PTSD after trauma. The importance of these regions in PTSD may be attributed to a pre-existing neurobiological risk factor, or neuromorphological changes after trauma precipitating emergent psychiatric illness. Our brain-behaviour relations provide support for the existing literature by highlighting the importance of the frontal lobe in the pathogenesis of PTSD. Future large-scale longitudinal studies including female participants may infer causal implications of atypical gyrification in PTSD and shed light on the potential effect of sex on this brain metric.

Quercetin abrogates bisphenol A induced altered neurobehavioral response and oxidative stress in zebrafish by modulating brain antioxidant defence system

Bisphenol A (BPA), a well-recognized anthropogenic xenoestrogen, has been identified as a causative agent responsible for inducing carcinogenicity, cognitive impairment, neurotoxicity, oxidative stress, etc. However, BPA-induced neurotoxicity and its possible amelioration through natural compound intervention remain elusive. The current study was performed to elucidate the neurotoxic potential of BPA in zebrafish (Danio rerio) by waterborne exposure and its possible amelioration by quercetin co-supplementation. Protective effect of quercetin against BPA-induced altered neurobehavioral response, oxidative stress and neuromorphological changes were evaluated in zebrafish brain. The present findings reveal that BPA-induced altered neurobehavioral response was ameliorated by quercetin. Biochemical studies advocate the potential therapeutic efficacy of quercetin against BPA-induced oxidative stress in zebrafish brain. Quercetin also shows neuroprotection against BPA-induced augmented neuronal pyknosis in periventricular grey zone (PGZ) of zebrafish brain. These basic findings indicate that quercetin may act as an effective intervention against BPA-induced neurotoxicity in zebrafish through down-regulation of oxidative stress.

From Child Abuse to Developing Borderline Personality Disorder Into Adulthood: Exploring the Neuromorphological and Epigenetic Pathway.

Borderline personality disorder (BPD) is one of the most common personality disorders seen in the general population. Among multiple identified risk factors, one of the most influential elements is exposure to an adverse childhood experience in terms of emotional, physical, or sexual abuse. A cascade of neuromorphological and epigenetic changes occurs in response to these childhood stressors, which may have a strong link to the development of BPD. PubMed and Google Scholar were searched for articles relevant to child abuse and the development of BPD. The search was not restricted to any time frame or geographic location. Significant epigenetic and neuromorphological changes are seen with child abuse, contributing to the development of BPD. Chronic stressors lead to hypothalamic-pituitary axis (HPA) activation, releasing cortisol that acts on the prefrontal cortex, amygdala, and hippocampus, producing the behavioral patterns seen in BPD. Overstimulation of gray matter leads to permanent neuromorphological changes, which can be visualized in functional MRI/brain scans. Hypermethylation of messenger ribonucleic acid in various sites suggests the impact of child abuse on the genetic level. Interestingly, the prevalence of BPD is seen equally in both genders but is diagnosed more frequently in females because they tend to be more likely to seek help. Understanding the impact of early age life stressors into adulthood calls for serious focus on early diagnosis and intervention. This implies the need for more studies in patients with BPD with or without any childhood traumatic experience and a better understanding of the changes that occur biopsychologically and genetically in response to trauma.

Neuromorphometric changes associated with photostimulated migratory phenotype in the Palaearctic-Indian male redheaded bunting.

Neural substrates, including brain areas, differential gene expression and neuroendocrine basis, of migration are known. However, very little is known about structural changes in the brain that underlie the development and cessation of migration in long-distance avian migrants. Towards this, we investigated neuromorphological changes in the higher-order associative areas in male redheaded bunting (Emberiza bruniceps), which is a Palaearctic-Indian night migrant with wintering grounds in India. Photosensitive birds (8L:16D; SD) were exposed to stimulatory long days (16L:8D; LD), with controls retained on non-stimulatory short days. LD birds depicted shifts to, and sustained night-time activity as recorded by actograms. LD birds demonstrated increased body mass, fat deposition and testicular volume in keeping with the migratory phenotype. When LD birds had exhibited 10.0 ± 2.4 cycles of Zugunruhe (intense nighttime activity in captives, akin to night migratory flight in the wild), bird brains were fixed by transcardial perfusion, and changes in the neuronal morphometry of pallial, sub-pallial and hypothalamic brain regions studied using rapid Golgi technique with modifications, as used and validated in our laboratory. There were significant differences in both area and perimeter of soma in the visual hyperpallium apicale implicated in migratory orientation and the neuroendocrine control region for timing of migration, the mediobasal hypothalamus. We attribute these neuromorphometric changes in the soma area and perimeter to the photostimulated changes associated with the development of migration and reproductive phenotypes in redheaded buntings. It is suggested that changes in the neuronal plasticity in brain control regions parallel photoperiod-induced physiological responses.

Gestational Exposure to Sodium Valproate Disrupts Fasciculation of the Mesotelencephalic Dopaminergic Tract, With a Selective Reduction of Dopaminergic Output From the Ventral Tegmental Area.

Gestational exposure to valproic acid (VPA) is known to cause behavioral deficits of sociability, matching similar alterations in human autism spectrum disorder (ASD). Available data are scarce on the neuromorphological changes in VPA-exposed animals. Here, we focused on alterations of the dopaminergic system, which is implicated in motivation and reward, with relevance to social cohesion. Whole brains from 7-day-old mice born to mothers given a single injection of VPA (400 mg/kg b.wt.) on E13.5 were immunostained against tyrosine hydroxylase (TH). They were scanned using the iDISCO method with a laser light-sheet microscope, and the reconstructed images were analyzed in 3D for quantitative morphometry. A marked reduction of mesotelencephalic (MT) axonal fascicles together with a widening of the MT tract were observed in VPA treated mice, while other major brain tracts appeared anatomically intact. We also found a reduction in the abundance of dopaminergic ventral tegmental (VTA) neurons, accompanied by diminished tissue level of DA in ventrobasal telencephalic regions (including the nucleus accumbens (NAc), olfactory tubercle, BST, substantia innominata). Such a reduction of DA was not observed in the non-limbic caudate-putamen. Conversely, the abundance of TH+ cells in the substantia nigra (SN) was increased, presumably due to a compensatory mechanism or to an altered distribution of TH+ neurons occupying the SN and the VTA. The findings suggest that defasciculation of the MT tract and neuronal loss in VTA, followed by diminished dopaminergic input to the ventrobasal telencephalon at a critical time point of embryonic development (E13-E14) may hinder the patterning of certain brain centers underlying decision making and sociability.

Emotional remodeling with oxytocin durably rescues trauma-induced behavioral and neuro-morphological changes in rats: a promising treatment for PTSD

Recent evidence indicates that reactivated memories are malleable and can integrate new information upon their reactivation. We injected rats with oxytocin to investigate whether the delivery of a drug which dampens anxiety and fear before the reactivation of trauma memory decreases the emotional load of the original representation and durably alleviates PTSD-like symptoms. Rats exposed to the single prolonged stress (SPS) model of PTSD were classified 15 and 17 days later as either resilient or vulnerable to trauma on the basis of their anxiety and arousal scores. Following 2 other weeks, they received an intracerebral infusion of oxytocin (0.1 µg/1 µL) or saline 40 min before their trauma memory was reactivated by exposure to SPS reminders. PTSD-like symptoms and reactivity to PTSD-related cues were examined 3–14 days after oxytocin treatment. Results showed that vulnerable rats treated with saline exhibited a robust PTSD syndrome including increased anxiety and decreased arousal, as well as intense fear reactions to SPS sensory and contextual cues. Exposure to a combination of those cues resulted in c-fos hypo-activation and dendritic arbor retraction in prefrontal cortex and amygdala neurons, relative to resilient rats. Remarkably, 83% of vulnerable rats subjected to oxytocin-based emotional remodeling exhibited a resilient phenotype, and SPS-induced morphological alterations in prelimbic cortex and basolateral amygdala were eliminated. Our findings emphasize the translational potential of the present oxytocin-based emotional remodeling protocol which, when administered even long after the trauma, produces deep re-processing of traumatic memories and durable attenuation of the PTSD symptomatology.

THE NEUROMORPHOLOGICAL CORRELATION OF RADIATION DOSE RATE

Relevance. Liquidators of consequences of the radiation accidents demonstrate increased rates of psychoneurological diseases after radiation exposure. However, the functional reorganization of brain neurons versus radiation exposure is insufficiently studied, thus precluding assessment of the pathogenesis of these diseases.Intention. To study neuromorphological correlates of low-dose radiation effects on brain neurons in radiobiological experiments.Methodology. In this GLP study, white outbred male rats (150 animals) at the age of 4 months were exposed to 0,5 Gy 60Co γ-rays at 0.5, 1.0, 2.5, 6.6 Gy/h. Age control group included animals with false exposure. Brain samples were taken 1 day, 6, 12, 18, 24 months after exposure. After conventional histologic processing, tinctorial properties, morphometric parameters, total protein and nucleic acids were assessed in neurons with subsequent mathematical modeling.Results and analysis. Normochromic neurons decreased linearly and their destructive forms increased over the observation period with increase in the irradiation dose. Among reversible changes, neurons in a state of inhibition and decreased functional activity predominated. The nerve cell index decreased over time, therefore some neurons died. Neuronal morphometry fluctuated, as well as their main structures, protein, cytoplasm and nucleolus RNA, nucleus DNA. With increasing dose rate, the changes became more expressed, and differed from the control group. These changes could be a basis for pathological processes in the brain.Conclusion. The ionizing radiation of studied range doesn’t cause significant organic changes of the brain neurons. However, under increasing radiation exposure the number of dysfunctional neurons linearly increases, as well as altered neurons. Almost all the neuromorphological parameters change, thus resulting in instability of structural – functional organization of neurons, with potential CNS disorders.

Vascular cognitive impairment and Alzheimer's disease: Is there a relationship between them?

Cognitive impairment (CI) associated with brain aging is a consequence of disorders varying in etiology and pathogenesis, which often coexist in elderly patients and can have a mutual impact on the clinical manifestation, severity, and rate of progression of CI. Alzheimer's disease (AD) and vascular CI are the most common forms of dementia in the elderly. In recent decades, there has been increasing evidence that there is a close relationship between these forms due to a substantial overlap of their risk factors, clinical manifestations, neuromorphological changes, as well as genetic and neuroimaging biomarkers. The complex multicomponent relationship of these disorders also makes it difficult to elaborate effective preventive and therapeutic approaches in these patients.

Using machine learning to understand neuromorphological change and image-based biomarker identification in Cavalier King Charles Spaniels with Chiari-like malformation-associated pain and syringomyelia.

BackgroundChiari‐like malformation (CM) is a complex malformation of the skull and cranial cervical vertebrae that potentially results in pain and secondary syringomyelia (SM). Chiari‐like malformation‐associated pain (CM‐P) can be challenging to diagnose. We propose a machine learning approach to characterize morphological changes in dogs that may or may not be apparent to human observers. This data‐driven approach can remove potential bias (or blindness) that may be produced by a hypothesis‐driven expert observer approach.Hypothesis/ObjectivesTo understand neuromorphological change and to identify image‐based biomarkers in dogs with CM‐P and symptomatic SM (SM‐S) using a novel machine learning approach, with the aim of increasing the understanding of these disorders.AnimalsThirty‐two client‐owned Cavalier King Charles Spaniels (CKCSs; 11 controls, 10 CM‐P, 11 SM‐S).MethodsRetrospective study using T2‐weighted midsagittal Digital Imaging and Communications in Medicine (DICOM) anonymized images, which then were mapped to images of an average clinically normal CKCS reference using Demons image registration. Key deformation features were automatically selected from the resulting deformation maps. A kernelized support vector machine was used for classifying characteristic localized changes in morphology.ResultsCandidate biomarkers were identified with receiver operating characteristic curves with area under the curve (AUC) of 0.78 (sensitivity 82%; specificity 69%) for the CM‐P biomarkers collectively and an AUC of 0.82 (sensitivity, 93%; specificity, 67%) for the SM‐S biomarkers, collectively.Conclusions and clinical importanceMachine learning techniques can assist CM/SM diagnosis and facilitate understanding of abnormal morphology location with the potential to be applied to a variety of breeds and conformational diseases.

Experimental Traumatic Brain Injury during Adolescence Enhances Cocaine Rewarding Efficacy and Dysregulates Dopamine and Neuroimmune Systems in Brain Reward Substrates.

Although clinical studies identify traumatic brain injury (TBI) as a risk factor for the development of substance use disorder, much remains unknown about the possible underlying pathogenesis and age-specific effects. Thus, the aim of this study is to test the hypothesis that at an age of ongoing maturation, adolescent TBI alters elements of the reward pathway, resulting in increased sensitivity to the rewarding effects of a subthreshold dose of cocaine that does not induce significant behavioral changes in naïve, non-injured mice. Specifically, these results were derived from the combination of the controlled cortical impact model of TBI, performed on either adolescent (6 weeks) or young adult (8 weeks) mice, followed by the cocaine-induced conditioned place preference assay 2 weeks later. Using three-dimensional isosurface rendering and volumetric image analysis, TBI was found to induce neuromorphological changes such as decreased dendritic complexity and reduced spine density in brain regions essential for reward perception and processing of drug-induced euphoria. Further, we demonstrated that these neuronal changes may affect the differential expression of dopamine-associated genes. Our analysis also provided evidence for age-related differences in immune response and the distinct involvement of augmented microglial phagocytic activity in the remodeling of neuronal structures in the adolescent TBI brain. Our studies suggest that TBI during adolescence, a period associated with ongoing maturation of dopaminergic systems, may subsequently enhance the abuse liability of cocaine in adulthood.

Comparative Evaluation of Neuromorphological Effects Under Single and Fractionated Irradiation in Small Doses

During the experiment, 180 mongrel male rats at the age of 4 months (corresponding to approximately 27-28 human years) were irradiated with γ-quanta 60Co with an energy of 1.2 MeV single and fractionated (in uniform portions for 5 days) in total doses of 50 cGy at a dose rate of 50 cGy/h. Neuromorphological changes of the sensorimotor cortex of the cerebral hemispheres in the III and V layers (respectively small and large pyramidal neurons) were studied.