Prenatal ethanol and cannabis exposure have sex- and region-specific effects on somatostatin and neuropeptide Y interneurons in the rat hippocampus.

BACKGROUND: Cannabis is increasingly being legalized and socially accepted around the world and is often used with alcohol in social settings. We recently showed that in utero exposure to both substances can alter the density of parvalbumin-expressing interneurons in the hippocampus. Here we investigate the effects of in utero alcohol and cannabis exposure, alone or in combination, on somatostatin- and neuropeptide Y-positive (NPY) interneurons. These are separate classes of interneurons important for network synchrony and inhibition in the hippocampus. METHODS: A 2 (Ethanol, Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague-Dawley rats to either ethanol or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5-20. Immunohistochemistry for somatostatin- and NPY-positive interneurons was performed in 50 µm tissue sections obtained at postnatal day 70. RESULTS: Exposure to THC in utero had region-specific and sex-specific effects on the density of somatostatin-positive interneurons in the adult rat hippocampus. A female-specific decrease in NPY interneuron cell density was observed in the CA1 region following THC exposure. Combined exposure to alcohol and THC reduced NPY neurons selectively in the ventral dentate gyrus hippocampal subfield. However, overall, co-exposure to alcohol and cannabis had neither additive nor synergistic effects on interneuron populations in other areas of the hippocampus. CONCLUSIONS: These results illustrate how alcohol and cannabis exposure in utero may affect hippocampal function by altering inhibitory processes in a sex-specific manner.

A Protocol for Remote Cognitive Training Developed for Use in Clinical Populations During the COVID-19 Pandemic.

Many traumatic brain injury (TBI) survivors face scheduling and transportation challenges when seeking therapeutic interventions. The COVID-19 pandemic created a shift in the use of at-home spaces for work, play, and research, inspiring the development of online therapeutic options. In the current study, we determined the feasibility of an at-home cognitive training tool (NeuroTrackerX) that uses anaglyph three-dimensional (3D) glasses and three-dimensional multiple object tracking (3D-MOT) software. We recruited 20 adults (10 female; mean age = 68.3 years, standard deviation [SD] = 6.75) as the at-home training group. We assessed cognitive health status for participants using a self-report questionnaire and the Mini-Mental State Examination (MMSE), and all participants were deemed cognitively healthy (MMSE >26). At-home participants loaned the necessary equipment (e.g., 3D glasses, computer equipment) from the research facilities and engaged in 10 training sessions over 5 weeks (two times per week). Participant recruitment, retention, adherence, and experience were used as markers of feasibility. For program validation, 20 participants (10 female; mean age = 63.39 years, SD = 12.22), who had previously completed at least eight sessions of the in-lab 3D-MOT program, were randomly selected as the control group. We assessed individual session scores, overall improvement, and learning rates between groups. Program feasibility is supported by high recruitment and retention, 90% participant adherence, and participants' ease of use of the program. Validation of the program is supported. Groups showed no differences in session scores (p > 0.05) and percentage improvement (p > 0.05) despite the differences in screen size and 3D technology. Participants in both groups showed significant improvements in task performance across the training sessions (p < 0.001). NeuroTrackerX provides a promising at-home option for cognitive training in cognitively healthy adults and may be a promising avenue as an at-home therapeutic for TBI survivors. This abstract was previously published on clinicaltrials.gov and can be found at: https://www.clinicaltrials.gov/ct2/show/NCT05278273.

Brain changes: aerobic exercise for traumatic brain injury rehabilitation.

Introduction: Traumatic Brain Injury (TBI) accounts for millions of hospitalizations and deaths worldwide. Aerobic exercise is an easily implementable, non-pharmacological intervention to treat TBI, however, there are no clear guidelines for how to best implement aerobic exercise treatment for TBI survivors across age and injury severity. Methods: We conducted a PRISMA-ScR to examine research on exercise interventions following TBI in children, youth and adults, spanning mild to severe TBI. Three electronic databases (PubMed, PsycInfo, and Web of Science) were searched systematically by two authors, using keywords delineated from "Traumatic Brain Injury," "Aerobic Exercise," and "Intervention." Results: Of the 415 papers originally identified from the search terms, 54 papers met the inclusion criteria and were included in this review. The papers were first grouped by participants' injury severity, and subdivided based on age at intervention, and time since injury where appropriate. Discussion: Aerobic exercise is a promising intervention for adolescent and adult TBI survivors, regardless of injury severity. However, research examining the benefits of post-injury aerobic exercise for children and older adults is lacking.

Prenatal alcohol and cannabis exposure can have opposing and region-specific effects on parvalbumin interneuron numbers in the hippocampus.

BACKGROUND: We recently showed that alcohol and cannabis can interact prenatally, and in a recent review paper, we identified parvalbumin-positive (PV) interneurons in the hippocampus as a potential point of convergence for these teratogens. METHODS: A 2 (Ethanol [EtOH], Air) × 2 (tetrahydrocannabinol [THC], Vehicle) design was used to expose pregnant Sprague-Dawley rats to either EtOH or air, in addition to either THC or the inhalant vehicle solution, during gestational days 5-20. Immunohistochemistry was performed to detect PV interneurons in 1 male and 1 female pup from each litter at postnatal day 70. RESULTS: Significant between-group and subregion-specific effects were found in the dorsal cornu ammonis 1 (CA1) subfield and the ventral dentate gyrus (DG). In the dorsal CA1 subfield, there was an increase in the number of PV interneurons in both the EtOH and EtOH +THC groups, but a decrease with THC alone. There were fewer changes in interneuron numbers overall in the DG, though there was a sex difference, with a decrease in the number of PV interneurons in the THC-exposed group in males. There was also a greater cell layer volume in the DG in the EtOH +THC group than the control group, and in the CA1 region in the EtOH group compared to the control and THC groups. CONCLUSIONS: Prenatal exposure to alcohol and THC differentially affects parvalbumin-positive interneuron numbers in the hippocampus, indicating that both individual and combined exposure can impact the balance of excitation and inhibition in a structure critically involved in learning and memory processes.

Understanding Changes in Hippocampal Interneurons Subtypes in the Pathogenesis of Alzheimer's Disease: A Systematic Review.

Background: It is becoming increasingly recognized that there is significant interneuron degeneration in Alzheimer's disease. As the hippocampus is integral for learning and memory, we performed a systematic review of primary literature focused on the relationship between Alzheimer's and hippocampal interneurons. In this study, we summarize the experimental work performed to date and identify opportunities for future experiments. Objectives: This PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-style systematic review seeks to summarize the findings of all accessible research focused on cholecystokinin (CCK), neuropeptide Y (NPY), parvalbumin (PV), and somatostatin (SOM) interneurons in the hippocampal formation. Results: One thousand five hundred ninety-three articles were pulled from PubMed, PsycInfo, and Web of Science, based on three blocks of search terms. There were 45 articles that met all the predetermined inclusion/exclusion criteria. There is strong evidence that PV interneurons are affected early in the disease by toxic amyloid beta (Aß) fragments; SOM interneurons are affected indirectly while the SOM neuropeptide may act to slowly worsen toxic Aß fragment accumulation, whereas NPY- and CCK-positive interneurons are affected later in the progression of the disease. Conclusions: Fewer studies have been performed on NPY and CCK interneurons, and there is room for further investigations regarding the role of PV interneurons in Alzheimer's to help resolve contradictory findings. This review found that PV interneurons are affected early in the disease, but only in Alzheimer's precursor protein but not tau models. NPY and CCK interneurons were found to be affected later in the disease, and SOM interneurons vary greatly. Future studies may consider reporting immunohistochemical studies inclusive of either cell location or morphology-as well as marker to give a more robust picture of the disease.

Heading in the Right Direction: A Critical Review of Studies Examining the Effects of Heading in Soccer Players.

The practice of heading in soccer has become a public concern because of the potential for subconcussive impacts to cause cumulative concussive-like effects; however, experimental evidence for this hypothesis has been mixed. This systematic review used pre-defined search parameters to assess primary literature that examined changes in cognitive, behavioral, structural, and/or biological processes after acute heading exposure in youth and young adult soccer players. The findings were synthesized into a concise and comprehensive summary of the research following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) format, and suggestions for standardization of acute heading protocols are described. A total of 1189 articles were considered for this review, with 19 articles meeting all of the inclusion criteria for full analysis. An attempt was made to identify methods with significant sensitivity and reliability by grouping studies based on their outcome measures. Because of lack of standardization across intervention types and data collection protocols, no sensitive and reliable methods could be identified conclusively to assess the effects of acute heading exposure in soccer players. Based on this review, there is not enough evidence to either support or refute the potential of effects of subconcussive events from acute soccer heading exposure. Recommendations for standardization of acute heading exposure studies based on the included literature are discussed. Standardization is required to better understand the impact of acute heading exposure in soccer players, while allowing for the development of guidelines that mitigate any potential risks and allowing athletes to remain active and develop their skills.

Does Mild Traumatic Brain Injury Increase the Risk for Dementia? A Systematic Review and Meta-Analysis.

BACKGROUND: Mild traumatic brain injury (mTBI) is a putative risk factor for dementia; however, despite having apparent face validity, the evidence supporting this hypothesis remains inconclusive. Understanding the role of mTBI as a risk factor is becoming increasingly important given the high prevalence of mTBI, and the increasing societal burden of dementia. OBJECTIVE: Our objective was to use the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) format to determine if an association exists between mTBI and dementia and related factors, and to quantify the degree of risk. METHODS: In this format, two authors conducted independent database searches of PubMed, PsycInfo, and CINAHL using three search blocks to find relevant papers published between 2000 and 2020. Relevant studies were selected using pre-defined inclusion/exclusion criteria, and bias scoring was performed independently by the two authors before a subset of studies was selected for meta-analysis. Twenty-one studies met the inclusion criteria for this systematic review. RESULTS: The meta-analysis yielded a pooled odds ratio of 1.96 (95% CI 1.698-2.263), meaning individuals were 1.96 times more likely to be diagnosed with dementia if they had a prior mTBI. Most studies examining neuropsychiatric and neuroimaging correlates of dementia found subtle, persistent changes after mTBI. CONCLUSION: These results indicate that mTBI is a risk factor for the development of dementia and causes subtle changes in performance on neuropsychiatric testing and brain structure in some patients.

A Systematic Review of the Effects of Perinatal Alcohol Exposure and Perinatal Marijuana Exposure on Adult Neurogenesis in the Dentate Gyrus.

BACKGROUND: Marijuana and alcohol are both substances that, when used during pregnancy, may have profound effects on the developing fetus. There is evidence to suggest that both drugs have the capacity to affect working memory, one function of the hippocampal formation; however, there is a paucity of data on how perinatal exposure to alcohol or cannabis impacts the process of adult neurogenesis. METHODS: This systematic review examines immunohistochemical data from adult rat and mouse models that assess perinatal alcohol or perinatal marijuana exposure. A comprehensive list of search terms was designed and used to search 3 separate databases. All results were imported to Mendeley and screened by 2 authors. Consensus was reached on a set of final papers that met the inclusion criteria, and their results were summarized. RESULTS: Twelve papers were identified as relevant, 10 of which pertained to the effects of perinatal alcohol on the adult hippocampus, and 2 pertained to the effects of perinatal marijuana on the adult hippocampus. Cellular proliferation in the dentate gyrus was not affected in adult rats and mice exposed to alcohol perinatally. In general, perinatal alcohol exposure did not have a significant and reliable effect on the maturation and survival of adult born granule neurons in the dentate gyrus. In contrast, interneuron numbers appear to be reduced in the dentate gyrus of adult rats and mice exposed perinatally to alcohol. Perinatal marijuana exposure was also found to reduce inhibitory interneuron numbers in the dentate gyrus. CONCLUSIONS: Perinatal alcohol exposure and perinatal marijuana exposure both act on inhibitory interneurons in the hippocampal formation of adult rats. These findings suggest simultaneous perinatal alcohol and marijuana exposure (SAM) may have a dramatic impact on inhibitory processes in the dentate gyrus.

Multiple Object Tracking Scores Predict Post-Concussion Status Years after Mild Traumatic Brain Injury.

The diagnosis of concussion remains challenging, particularly in cases where several months have passed between a traumatic brain injury (TBI) and clinical assessment. Tracking multiple moving objects in three-dimensional (3D) space engages many of the same cognitive processes that are affected by concussion, a form of mild TBI (mTBI), suggesting that tests of 3D multiple object tracking (3D-MOT) may be sensitive to post-concussion syndrome (PCS) after a brain injury has occurred. To test this, we evaluated 3D-MOT performance (using NeuroTrackerTM) against Sports Concussion Assessment Tool results for cognition, balance, and symptom severity in a large sample (N = 457) of male and female participants between the ages of 6 and 73 years. 3D-MOT performance in subjects under age 13 was not impaired by a history of concussion, but was positively associated with cognition and balance. 3D-MOT performance in those 13 and older was negatively associated with concussion symptom severity and positively associated with cognition and balance. 3D-MOT was selectively impaired in subjects with probable PCS (pPCS), defined using the 95th percentile of symptom severity for subjects with no history of concussion. A decision tree predicted concussion status with 95.2% overall test accuracy (91.1% sensitivity, 97.8% specificity), using concussion history, age, and 3D-MOT score. Persons with a history of concussion in the past 37 days were predicted to have pPCS if they were ≥35 years of age, or if they were <35 years of age but achieved scores below 1.2 on the 3D-MOT. These results demonstrate the potential of 3D-MOT for pPCS diagnosis and highlight the increased vulnerability to concussion symptoms that comes with age.