Biology subjects

Grigoletti-Lima, G. B.

Publications and source records attributed to Grigoletti-Lima, G. B..

3 recordsLinked to original sources

bioRxiv2026

EARLY-LIFE STRESS INDUCES SEXUALLY DIMORPHIC BRAIN AGING VIA MESOLIMBIC ALTERATIONS AND FRONTO-STRIATAL DYSFUNCTION

Prenatal stress influences brain development; however, its long-term, region-specific effects on brain aging in males and females remain insufficiently characterized. This study examined the impact of unpredictable mild prenatal stress on behavior, cognition, and maternal care in C57BL/6J mice at middle (12 months) and old (18 months) ages. Stressed dams showed fragmented, unpredictable maternal behaviors, creating a stressful postnatal environment without impairing caregiving capacity. Both male and female offspring were born with lower birth weights and showed rapid postnatal growth, a trajectory associated with central insulin resistance and hippocampal signaling deficits. Sex-specific behavioral differences emerged with age. Middle-aged stressed males exhibited anhedonia, which progressed to hyperactivity, stereotypy, and persistent spatial memory deficits in old age. These outcomes corresponded with accelerated fronto-striatal decline, likely mediated by insulin resistance and increased rigidity of medial prefrontal cortex structures due to diminished local estrogenic activity. In contrast, middle-aged stressed females displayed hypoactivity and reduced anxiety, later developing anhedonia in old age while maintaining hippocampus-dependent memory. In females, this pattern supports a model in which a neuroestrogen - and growth factor-dependent feedback loop transiently preserves hippocampal plasticity but compromises dopaminergic function in reward circuits. This balance may deteriorate with reproductive senescence. Both sexes retained cognitive flexibility, indicating domain-specific rather than global cognitive impairment. These findings demonstrate that excessive prenatal glucocorticoid exposure and unpredictable postnatal care produce a combined hormonal and metabolic insult, resulting in sexually divergent trajectories of brain aging. The results underscore the necessity of incorporating sex as a biological variable in fetal programming research across the lifespan.

neuroscience↗

bioRxiv2024

Enriched environmental intervention mitigates hippocampal cellularity and behavioral disorders in maternal protein-restricted male rat offspring

BackgroundGestational protein intake restriction induces long-lasting harmful outcomes in the offsprings organs and systems. AimsThis study sought to evaluate the effects of protein restriction during pregnancy and breastfeeding in 42-day-old male offspring on the structure of the hippocampus, behavior tests related to memory and emotions, and the influence of an enriched environment on these parameters. Results and DiscussionThe current study demonstrated that maternal protein restriction during neural development causes crucial morphological changes in the hippocampus, making the LP offspring vulnerable to specific neural disorders in adulthood. In addition, it supports the selfish brain theory, a paradigm that postulates the brain maintains its mass selfishly by reallocating resources from other body parts when faced with nutritional stress. However, the hippocampus cellularity pattern was profoundly altered, significantly reducing the number of neurons after the breastfeeding period. This may expand the understanding of nutritional stress affecting the brain areas constitution and its supposed effects on posterior behavioral disorders. Here, reciprocal data was observed between brain masses, changes in the hippocampus cell pattern, and decreased body mass in the LP progeny. In conclusion it was demonstrated that neuronal composition and structure profoundly modified by dietary restriction are surprisingly restored from primordial cells by exposure to the enriched environment. In addition, we must emphasize that although we have observed a significant reduction in the number of neurons after gestational and breastfeeding periods, we demonstrated for the first time a substantial reduction in the fear-reflecting behavior, which an enriched environment exposure may revert. The enriched environment also significantly modified the discrimination ratio, increasing the ability of both progenies to discriminate between novel and familiar objects in a short time associated with reverse abnormal hippocampus cell patterns. These findings underscore the potential for environmental interventions to mitigate the effects of early=life nutritional stress on brain development and behavior.

animal behavior and cognition↗

bioRxiv2021

Precocious hippocampal structural and functional changes in gestational protein-restricted male elderly offspring: an Alzheimer-simile disease model?

BackgroundMaternal undernutrition has been associated with psychiatric and neurological disorders characterized by learning and memory impairment. Considering the lack of evidence for this, we aimed to analyze the effects of gestational protein restriction on learning and memory function later in life. This research associates behavioral findings with hippocampal cell numbers and protein content related to neurodegenerative brain disease. MethodsExperiments were conducted in animals subjected to a low-protein (LP, 6% casein) or regular-protein (NP, 17% casein) diet throughout their pregnancy. Behavioral tests, isolated hippocampal isotropic fractionator cell studies, immunoblotting, and survival lifetime tests were performed. The results confirmed that the birthweight of LP male pups significantly reduced relative to NP male pups and that hippocampal mass increased in 88-week-old LP compared to age-matched NP offspring. We used the Morris water maze proximity measure, which is the sum of 10 distances each second between rat position and location of a hidden platform target, as a suitable test for assessing age-related learning or memory impairment in aged offspring. ResultsThe results showed an increased proximity measure in 87-week-old LP rats (52.6 x 104 {+/-} 10.3 x 104 mm) as compared to NP rats (47.0 x 104 {+/-} 10.6 x 103 mm, p = 0.0007). In addition, LP rats exhibited anxiety-like behaviors compared to NP rats at 48 and 86 weeks of life. Additionally, the estimated neuron number was unaltered in LP rats; however, glial and other cell numbers increased in LP compared to NP rats. Here, we showed unprecedented hippocampal deposition of brain-derived neurotrophic factor, {beta}-amyloid peptide (A{beta}), and tau protein in 88-week-old LP compared to age-matched NP offspring. To date, no predicted studies showed changes in hippocampal neuron and glial cell numbers in maternal protein-restricted elderly offspring. The current data suggest that maternal protein restriction has a high impact on lifespan and brain structure, and function. Conclusionthe gestational protein restriction may accelerate hippocampal function loss, impacting learning/memory performance, and supposedly developing diseases similar to Alzheimers disease (AD) in elderly offspring. Thus, we propose that maternal protein restriction could be a probable, elegant, and novel method for constructing an AD-like model in adult male offspring.

developmental biology↗