Biology subjects

Cabeza, L.

Publications and source records attributed to Cabeza, L..

4 recordsLinked to original sources

bioRxiv2025

Novel fat-taste enhancers modulate functional connectivity of the reward system following sustained activation of gustatory pathways in mice

Humans and rodents exhibit an innate preference for dietary fat, and dysfunction of lingual fat-taste receptors CD36 and GPR120 in obesity suggests that impaired oro-sensory lipid detection may contribute to its development. Rodent models with reduced fat-taste sensitivity display increased fat intake, highlighting the role of taste perception in dietary regulation. The newly developed NKS-3 and NKS-5, high-affinity agonists for CD36 and CD36/GPR120 receptors, respectively, induce early fat satiation and reduce both fat-rich food intake and body weight gain in diet-induced obese mice. However, the neural mechanisms underlying these effects remain unclear. Here, we investigated the response of the reward system to a sustained activation of CD36 and GPR120 via fat-taste enhancers NKS-3 and NKS-5 compared to linoleic acid (LA). Male C57BL/6JRj mice (N=88) received oral administration of vehicle, 0.2% LA, 50 {micro}M NKS-3 or 75 {micro}M NKS-5 for 10 days. The immunohistochemical analysis of cerebral FosB neuronal expression revealed a reorganization of the functional network connectivity. Behavioral assessments over an additional 10-day period in a second cohort of animals detected no adverse motivational, compulsive-like, depressive or anxiogenic effect of the treatments. Our findings suggest that our fat-taste enhancers may offer a promising therapeutic strategy against obesity, leveraging the oral-gut-brain axis to regulate fat-rich food intake.

neuroscience↗

bioRxiv2024

Neurovascular unit adjustments following chronic distress explain motivational deficits in mice

BackgroundThe neurovascular unit (NVU) represents the structural and functional relationship between the neural tissue and the blood. Neurovascular dysfunction has been highlighted in neuropsychiatric afflictions, but whether it is a cause or a consequence of the pathology remains to be elucidated. Thus, to elucidate the role of the NVU on the emergence of emotional-cognitive dysfunction, it is necessary to study how its individual components associate. This study therefore aims at investigating whether the development of depressive-related loss of motivation is grounded on NVU adjustments impacting the permeability of the blood-brain barrier (BBB) and in particular, of the structural scaffolding of microvessels. MethodsAdult male C57BL/6jRj mice chronically treated with corticosterone (CORT) and showing severe motivational deficits in an operant progressive ratio (PR) schedule of reinforcement task, presented altered neural activation assessed through FosB expression in key brain regions involved in motivational processing (anterior insular cortex, basolateral amygdala, bed nucleus of the stria terminalis and ventral tegmental area). We evaluated NVU modifications through immunofluorescence staining targeting specific markers of microglia (IBA-1), endothelial tight junctions (ZO-1) and astrocytes (GFAP). The effect of chronic CORT administration on mice BBB permeability was evaluated through in vivo perfusion of fluorescent 40 kDa Dextran. ResultsOur results highlight that where sustained neuronal activation failed, NVU modifications predict behavioural deficits in CORT-treated animals. Notably, our analyses show that NVU modifications within the ventral tegmental area are essential to understand effort-based related behavioural performance in mice, and most particularly, that the key element of microvessels tight junctions ZO-1 plays a pivotal role on motivation-related behavioural output. ConclusionsOur results confirm a direct role of neurovascular adaptations on emotional and cognitive behavioural performance in mice, and therefore place the NVU in a key position in the research of the biological substrate at the origin of neuropsychiatric disorders.

neuroscience↗

bioRxiv2023

Linoleic acid supplementation reverses microglial response to diet induced-obesity at hypothalamic, cortical and subcortical level in mice

Obesity is a major risk factor for neuropsychiatric alterations. Fatty regimes lead to systemic and cerebral inflammation, the latest acting through lipotoxicity on hypothalamic structures controlling energy homeostasis. Since literature points to a protective effect of linoleic acid (LA) on mood disorders through the regulation of systemic inflammation, we investigated how five weeks of LA supplementation modulates emotional behaviour and microglia-related neuroinflammation. C57BL/6j mice were fed with either a high-fat (HFD) or a standard diet for 12 weeks, underwent a battery of behavioural tests and were subsequently sacrificed for immunofluorescence staining targeting microglia-specific calcium-binding proteins (IBA-1). Neuroinflammation severity was approximated in multiple hypothalamic, cortical and subcortical regions. Our results show an anxio-depressive-like effect of sustained HFD that neither was alleviated nor worsen with LA supplementation. Increased IBA-1 expression in the HFD group was substantially reversed with LA supplementation. Thus, our results suggest anti-neuroinflammatory properties of LA not restricted to hypothalamic areas, but also evident at the cortical and subcortical level. This study is therefore relevant in the frame of obesity and neuropsychiatric disorders with a neuroinflammatory basis. Further investigation may provide more information to justify dietary strategies aiming at reducing the impact of obesity associated comorbidities.

neuroscience↗

bioRxiv2021

Chronic distress in male mice impairs motivation compromising both effort and reward processing with altered anterior insular cortex and basolateral amygdala neural activation

In humans and mammals, effort-based decision-making for monetary or food rewards paradigms contribute to the study of adaptive goal-directed behaviours acquired through reinforcement learning. Chronic distress modelled by repeated exposure to glucocorticoids in rodents induces suboptimal decision-making under uncertainty by impinging on instrumental acquisition and prompting negative valence behaviours. In order to further disentangle the motivational tenets of adaptive decision-making, this study addressed the consequences of enduring distress on relevant effort and reward processing dimensions. Experimentally, appetitive and consummatory components of motivation were evaluated in adult C57BL/6JRj male mice experiencing chronic distress induced by oral corticosterone (CORT), using multiple complementary discrete behavioural tests. Behavioural data (from Novelty Supressed Feeding, operant effort-based choice, Free Feeding and Sucrose Preference tasks) collectively show that behavioural initiation, effort allocation and hedonic appreciation and valuation are altered in mice exposed to several weeks of oral CORT treatment. Additionally, data analysis from FosB immunohistochemical processing of postmortem brain samples highlight a CORT-dependent dampening of neural activation in the anterior insular cortex (aIC) and basolateral amygdala (BLA), key telencephalic brain regions involved in cue appetitive and consummatory motivational processing. Combined, these results suggest that chronic distress-induced irregular aIC and BLA neural activations with reduced effort production and attenuated reward value processing during reinforcement-based instrumental learning could result in maladaptive decision-making under uncertainty. The current study further illustrates how the stoichiometry of effort and reward processing contributes to dynamically adjust the motivational threshold triggering goal-directed behaviours in versatile environments.

neuroscience↗