Biology subjects

Reichelt, A. C.

Publications and source records attributed to Reichelt, A. C..

6 recordsLinked to original sources

bioRxiv2024

Elevated body mass index in youth is associated with dysregulated surrogate markers of neural inhibition & excitation, and internetwork functional dysconnectivity

The developing child and adolescent brain is thought to have an increased vulnerability to the negative impact of obesity and excessive consumption of hyperpalatable and energy-rich foods. In this study, we investigated the neurophysiological effects of overweight and obesity in 30 participants spanning childhood and adolescence (8-19 years), using a naturalistic viewing paradigm with Inscapes, in a pseudo-resting-state protocol scan with magnetoencephalography (MEG). Subjects were median split on body mass indices (BMI), categorised into two groups comprising: lower <25 kg/m2 (n=15) and higher [≥]25 kg/m2 (n=15). We assessed spontaneous, regional neural function indexed by oscillatory activity, and functional connectivity within and between intrinsic resting brain networks, including the default mode network, dorsal and ventral attention, somatomotor, visual, language, central executive and salience networks. Elevated BMI was associated with significant reductions in activity of the posterior dominant rhythm, and gamma hyperactivity across widespread cortical areas, suggesting intrinsic neuronal hyperexcitability and disinhibition in children and adolescents. Additionally, we observed low-frequency theta hypoconnectivity between resting state networks including the salience, visual, and default mode networks, and overall reduced global efficiency in brain network structure, suggesting reduced effectiveness in neural communication. These findings underscore the neural impact of body composition on the developing brain, suggesting deleterious alterations in excitation and inhibition from surrogate neural markers associated with neurochemistry and brain networks linked with cognitive and behavioural functioning. These alterations may contribute to the persistent behavioural rigidity and difficulties in adopting healthier eating behaviours into adulthood.

neuroscience↗

bioRxiv2021

Intergenerational effects of a paternal Western diet during adolescence on offspring gut microbiota, stress reactivity and social behavior

The global consumption of highly processed, calorie-dense foods has contributed to an epidemic of overweight and obesity, along with negative consequences for metabolic dysfunction and disease susceptibility. As it becomes apparent that overweight and obesity have ripple effects through generations, understanding of the processes involved is required, in both maternal and paternal epigenetic inheritance. We focused on the patrilineal effects of a Western-style high-fat (21%) and high-sugar (34%) diet (WD) compared to control diet (CD) during adolescence and investigated F0 and F1 mice for physiological and behavioral changes. F0 males (fathers) showed increased body weight, impaired glycemic control, and decreased attractiveness to females. Paternal WD caused significant phenotypic changes in F1 offspring, including higher body weights of pups, increased Actinobacteria abundance in the gut microbiota (ascertained using 16S microbiome profiling), a food preference for WD pellets, increased male dominance and attractiveness to females, as well as decreased behavioral despair. These results collectively demonstrate the long-term intergenerational effects of a Western-style diet during paternal adolescence. The behavioral and physiological alterations in F1 offspring provide evidence of adaptive paternal programming via epigenetic inheritance. These findings have important implications for understanding paternally mediated intergenerational inheritance, and its relevance to offspring health and disease susceptibility.

neuroscience↗

bioRxiv2019

A high-fat high-sugar diet in adolescent rats impairs social memory and alters chemical markers characteristic of atypical neuroplasticity and GABAergic neurodevelopment in the medial prefrontal cortex

Brain plasticity is a multifaceted process that is dependent on both neurons and extracellular matrix (ECM) structures, including perineuronal nets (PNNs). In the medial prefrontal cortex (mPFC) PNNs primarily surround fast-spiking parvalbumin (PV)-containing GABAergic interneurons and are central to regulation of neuroplasticity. In addition to the development of obesity, high-fat and high-sugar (HFHS) diets are also associated with alterations in brain plasticity and emotional behaviours in humans. To examine the underlying involvement of PNNs and cortical plasticity in the mPFC in diet-evoked social behaviour deficits (in this case social recognition), we exposed adolescent (postnatal days P28-P56) rats to a HFHS-supplemented diet. At P56 HFHS-fed animals and age-matched controls fed standard chow were euthanized and co-localization of PNNs with PV neurons in the prelimbic (PrL) and infralimbic (IL) and anterior cingulate (ACC) sub regions of the PFC were examined by dual fluorescence immunohistochemistry. {Delta}FosB expression was also assessed as a measure of chronic activity and behavioural addiction marker. Consumption of the HFHS diet reduced the number of PV+ neurons and PNNs in the infralimbic (IL) region of the mPFC by -21.9% and -16.5%, respectively. While PV+ neurons and PNNs were not significantly decreased in the ACC or PrL, the percentage of PV+ and PNN co-expressing neurons was increased in all assessed regions of the mPFC in HFHS-fed rats (+33.7% to +41.3%). This shows that the population of PV neurons remaining are those surrounded by PNNs, which may afford some protection against HFHS diet-induced mPFC-dysregulation. {Delta}FosB expression showed a 5-10-fold increase (p < 0.001) in each mPFC region, supporting the hypothesis that a HFHS diet induces mPFC dysfunction and subsequent behavioural deficits. The data presented shows a potential neurophysiological mechanism and response to specific diet-evoked social recognition deficits as a result of hypercaloric intake in adolescence.

neuroscience↗

bioRxiv2018

An intermittent hypercaloric diet alters gut microbiota, prefrontal cortical gene expression and social behaviours in rats

Excessive consumption of high fat and high sugar (HFHS) diets are known to alter reward processing and aspects of behaviour, and change microbiota profiles. Studies in gnotobiotic mice also provide evidence that gut microorganisms influence social behaviour. To further investigate these interactions, the impact of intermittent access to a HFHS diet on social behaviour, gene expression and microbiota composition was examined. Rats were permitted intermittent daily access (2h / day) to a palatable HFHS diet for 28 days across the adolescent period. Social interaction, social memory and novel object recognition were assessed during this period. Following testing, RT-PCR was conducted on hippocampal and prefrontal cortex (PFC) samples. 16S ribosomal RNA amplicon sequencing was used for identification and relative quantification of bacterial taxa. Reduced social interaction behaviours, and impaired social memory and novel object recognition were observed in HFHS diet rats. Reduced levels of monoamine oxidase A (Maoa), catechol-O-methyltransferase (Comt) and brain derived neurotrophic factor (Bdnf) mRNA were observed in the PFC of HFHS diet rats. The relative abundance of a number of specific taxa differed significantly between the two diet groups, in particular, Lachnospiraceae and Ruminoccoceae bacteria, which also predicted social behaviours, novel object recognition performance and Maoa expression. This is the first study to show that limited daily access to HFHS diet alters social behaviour and cognition in rats. Furthermore, behavioural changes are associated with alterations to cortical gene expression of enzymes involved in monoamine synthesis and neuroplasticity, and microbiota profiles predicted diet-induced changes to behaviour and gene expression.

neuroscience↗

bioRxiv2018

Sucrose or sucrose and caffeine differentially impact memory and anxiety like behaviours, and alter hippocampal parvalbumin and doublecortin

Caffeinated sugar-sweetened \"energy\" drinks are a subset of soft drinks that are popular among young people worldwide. High sucrose diets impair cognition and alter aspects of emotional behaviour in rats, however, little is known about sucrose combined with caffeine. Rats were allocated to 2h/day 10% sucrose (Suc), 10% sucrose plus 0.04% caffeine (CafSuc) or control (water) conditions. The addition of caffeine to sucrose appeared to increase the rewarding aspect of sucrose, as the CafSuc group consumed more solution than the Suc group. After 14 days of intermittent Suc or CafSuc access, anxiety was assessed in the elevated plus maze (EPM) prior to their daily solution access, whereby CafSuc and Suc rats spent more time in the closed arms, indicative of increased anxiety. Following daily solution access, CafSuc, but not Suc, rats showed reduced anxiety-like behaviour in the open-field. Control and CafSuc rats displayed intact place and long-term object memory, while Suc showed impaired memory performance. Sucrose reduced parvalbumin immunoreactivity in the hippocampus, but no differences were observed between Control and CafSuc conditions. Parvalbumin reactivity in the basolateral amygdala did not differ between conditions. Reduced doublecortin immunoreactivity in the dentate gyrus relative to controls was seen in the CafSuc, but not Suc, treatment condition. These findings indicate that the addition of caffeine to sucrose attenuates cognitive deficits. However, the addition of caffeine to sucrose evokes anxiety-like responses under certain testing conditions, suggesting that frequent consumption of caffeinated energy drinks may promote emotional alterations and brain changes compared to standard soft drinks.

neuroscience↗

bioRxiv2018

Within-subject combination of diffusion tensor MRI and CLARITY reveals alterations in the social brain network resulting from α-neurexin II deletion

BackgroundOf the many genetic mutations known to increase the risk of autism spectrum disorder, a large proportion cluster upon synaptic proteins. One such family of presynaptic proteins are the neurexins (NRXN), and recent genetic and mouse evidence has suggested a causative role for NRXN2 in generating altered social behaviours. Autism has been conceptualised as a disorder of atypical connectivity, yet how single-gene mutations affect such connectivity remains under-explored. To attempt to address this, we have developed a quantitative analysis of microstructure and structural connectivity leveraging diffusion tensor MRI (DTI) with high-resolution 3D imaging in optically cleared (CLARITY) brain tissue in the same mouse, applied here to the Nrxn2 knockout (KO) model. MethodsFixed brains of Nrxn2 KO mice underwent DTI using 9.4T MRI, and diffusion properties of socially-relevant brain regions were quantified. The same tissue was then subjected to CLARITY to immunolabel axons and cell bodies, which were also quantified. ResultsDTI revealed decreases in fractional anisotropy and increases in apparent diffusion coefficient in the amygdala (including the basolateral nuclei), the anterior cingulate cortex, the orbitofrontal cortex and the hippocampus. Radial diffusivity of the anterior cingulate cortex and orbitofrontal cortex was significantly increased in Nrxn2 KO mice, as were tracts between the amygdala and the orbitofrontal cortex. Using CLARITY, we find significantly altered axonal orientation in the amygdala, orbitofrontal cortex and the anterior cingulate cortex, which was unrelated to cell density. ConclusionsOur findings demonstrate that deleting a single neurexin gene (Nrxn2) induces atypical structural connectivity within socially-relevant brain regions. More generally, our combined within-subject DTI and CLARITY approach presents a new, more sensitive method of revealing hitherto undetectable differences in the autistic brain.

neuroscience↗