Biology subjects

Kovacs-Balint, Z.

Publications and source records attributed to Kovacs-Balint, Z..

4 recordsLinked to original sources

bioRxiv2025

Structural Effects of Low Social Status and Obesogenic Diet on Social and Emotional Neurocircuits in Female Macaques: A Longitudinal Study from Infancy to Adulthood

A substantial body of literature has demonstrated a consistent link between psychosocial stress and obesity in children, particularly in those from low socioeconomic backgrounds. Despite evidence indicating a complex interplay between stress, diet and obesity, there is a limited understanding of the specific versus potentially synergistic effects of obesity and stress on brain structural and functional development. This study investigates the developmental and long-term brain structural alterations resulting from exposure to chronic social stress due to low (subordinate -SUB-) social status and postnatal obesogenic diets. Forty-one female rhesus macaques (Dominants -DOM-, n=21; Subordinates -SUB-, n=20) were assigned to either only low-calorie diet (LCD) or to both high-calorie diet (HCD) and LCD (Choice diet) from birth through the juvenile period. After menarche, all subjects were maintained on a LCD-only diet through adulthood. Twenty-seven animals (DOM: n=13, SUB: n=14) were studied again in adulthood to investigate the long-term effects of early diet and social rank on brain structure. Cumulative Kcal consumption was measured from birth through 16 months and body weights were measured at all time points. Overall, the findings show specific effects of obesogenic diet and psychosocial stress on cortical and corticolimbic brain regions. Animals with access to the obesogenic diet had larger overall brain size (measured as intracranial volume -ICV-) and larger overall volumes of prefrontal cortex, insula, superior temporal sulcus (defined as temporo-parieto-occipital area rostral and caudal regions (TPOr and TPOc)) than those in the low-calorie diet. Most of these regional diet effects, except for the insula, were driven by general effects of the diet on brain size. The diet effects were lost when adding the adult data to the longitudinal analysis, suggesting transient effects of obesogenic diets while the animals were consuming it, but not long-term, persistent effects. These findings highlight the potential of brain rescue mechanisms that could offset lasting developmental effects of early-life obesogenic diet consumption. With respect to social rank, SUB exhibited larger volumes in brain regions related to social cognition and emotional processing than DOM animals. When the adult data was added to the longitudinal analysis, the effects of social rank were prominent in the hippocampus, superior temporal sulcus, temporo-parieto-occipital rostral region, and the temporal auditory cortices after ICV data correction, suggesting long-term, persistent and cumulative effects of these social experiences, in contrast to the transient diet effects.

neuroscience↗

bioRxiv2020

Validation of the Social Responsiveness Scale (SRS) to screen for atypical social behaviors in juvenile macaques

Primates form strong social bonds and depend on social relationships and networks that provide shared resources and protection critical for survival. Social deficits such as those present in autism spectrum disorder (ASD) and other psychiatric disorders hinder the individual’s functioning in communities. Given that early diagnosis and intervention can improve outcomes and trajectories of ASD, there is a great need for tools to identify early markers for screening/diagnosis, and for translational animal models to uncover biological mechanisms and develop treatments. One of the most widely used screening tools for ASD in children is the Social Responsiveness Scale (SRS), a quantitative measure used to identify individuals with atypical social behaviors. The SRS has been adapted for use in adult rhesus monkeys (Macaca mulatta) –a species very close to humans in terms of social behavior, brain anatomy/connectivity and development– but has not yet been validated or adapted for a necessary downward extension to younger ages matching those for ASD diagnosis in children. The goal of the present study was to adapt and validate the adult macaque SRS (mSRS) in juvenile macaques with age equivalent to 4-6 yr old human children. Expert primate coders modified the mSRS to adapt it to rate atypical social behaviors in juvenile macaques living in complex social groups at the Yerkes National Primate Research Center. Construct and face validity of this juvenile mSRS (jmSRS) was determined based on well-established and operationalized measures of social and non-social behaviors in this species using traditional behavioral observations. We found that the jmSRS identifies variability in social responsiveness of juvenile rhesus monkeys and shows strong construct/predictive validity, as well as sensitivity to detect atypical social behaviors in young male and female macaques across social status. Thus, the jmSRS provides a promising tool for translational research on macaque models of children social disorders.View Full Text

animal behavior and cognition↗

bioRxiv2019

Long-term alterations in brain and behavior after postnatal Zika virus infections in infant macaques

Considering the impact that Zika virus (ZIKV) infection has on the fetal nervous system and given that the postnatal period is also a time of rapid brain growth, it is important to understand the potential neurobehavioral consequences of ZIKV infection during infancy. Postnatal ZIKV infection in a rhesus macaque (RM) model resulted in long-term behavioral, motor, and cognitive changes, including increased emotional reactivity, decreased social contact, loss of balance, and deficits in visual recognition memory at one year of age. Structural and functional MRI showed that ZIKV-infected infant RMs had persistent enlargement of lateral ventricles, smaller volumes and altered functional connectivity between brain areas important for socioemotional behavior, cognitive, and motor function (e.g. amygdala, hippocampus, cerebellum). Neuropathological changes corresponded with neuroimaging results and were consistent with the behavioral and memory deficits. Overall, this study demonstrates that postnatal ZIKV infection of infants in this model has long lasting neurodevelopmental consequences.

neuroscience↗

bioRxiv2019

Chemogenetic inhibition of the amygdala modulates emotional behavior expression in infant rhesus monkeys

Manipulation of neuronal activity during the early postnatal period in monkeys has been largely limited to permanent lesion studies, which can be impacted by developmental plasticity leading to reorganization and compensation from other brain structures that can interfere with the interpretations of results. Chemogenetic tools, such as DREADDs (designer receptors exclusively activated by designer drugs), can transiently and reversibly activate or inactivate brain structures, avoiding the pitfalls of permanent lesions to better address important developmental neuroscience questions. We demonstrate that inhibitory DREADDs in the amygdala can be used to manipulate socioemotional behavior in infant monkeys. Two infant rhesus monkeys (1 male, 1 female) received AAV5-hSyn-HA-hM4Di-IRES-mCitrine injections bilaterally in the amygdala at 9 months of age. DREADD activation after systemic administration of either clozapine-N-oxide or low dose clozapine resulted in decreased freezing and anxiety on the human intruder paradigm and changed the looking patterns on a socioemotional attention eyetracking task, compared to vehicle administration. The DREADD-induced behaviors were reminiscent of, but not identical to, those seen after permanent lesions of the amygdala in infant monkeys, such that early amygdala lesions produce a more extensive array of behavioral changes in response to the human intruder task that were not seen with DREADD-evoked inhibition of this region. Our results support the notion that early permanent damage leads to brain reorganization manifesting in a broader impact on behavior. The current study provides a proof-of-principle that DREADDs can be used in young infant monkeys to transiently and reversibly manipulate behavior. Statement of SignificanceMany neurodevelopmental disorders exhibit abnormal structural or functional amygdala development and alterations in socioemotional behavior. To date, developmental neuroscience studies have relied on permanent lesions techniques to investigate how atypical amygdala development impacts socioemotional behaviors, which may not adequately recapitulate the role of amygdala dysfunction in the manifestation of aberrant behavior. The present study sought to demonstrate that the DREADDs (designer receptors exclusively activated by designer drugs) chemogenetic tool could transiently inhibit amygdala activity in infant monkeys resulting in alterations in socioemotional behavior. This proof-of-principle study supports the use of chemogenetics for developmental neuroscience research, providing an opportunity to broaden our understanding of how changes in neuronal activity across early postnatal development influences behavior and clinical symptoms.

neuroscience↗