Biology subjects

Bakoyiannis, I.

Publications and source records attributed to Bakoyiannis, I..

3 recordsLinked to original sources

bioRxiv2025

Obesogenic diet impairs memory consolidation via the hippocampal endocannabinoid system

Although obesogenic high-fat/high-sugar diets impair memory function in humans and rodents, the underlying mechanisms remain elusive. Given that the brain endocannabinoid system and type-1 cannabinoid receptors (CB1R) control memory processes and are overactive under obesogenic conditions, we studied whether the effects of obesogenic diet consumption on memory function are dependent on this system. Using an object recognition memory (ORM) task in male mice, we showed that CB1R activity is required for obesogenic diet-induced impairment of long-term memory performance. This impairment was prevented by post-training systemic blockade of CB1R, which also normalized training-induced hippocampal cellular and synaptic overactivation. Consistently, obesogenic diet potentiated the increase of hippocampal endocannabinoid levels and enhanced CB1R expression induced by ORM, and genetic CB1R deletion from hippocampal glutamatergic neurons abolished diet-induced memory deficits. Strikingly, obesogenic diet enhanced the hippocampal mTOR pathway in a CB1R-dependent manner, and pharmacological mTOR inhibition after training rescued diet-induced ORM consolidation deficits. Together, these results establish how an obesogenic environment can lead to hippocampal overactivation of the endocannabinoid system and of the mTOR pathway to eventually impair memory consolidation. Thus, these results shed light on the mechanisms of diet-induced cognitive alterations and may pave the way to novel therapeutic strategies. HighlightsO_LIObesogenic diet induces long-term memory deficits, which are rescued by CB1R blockade C_LIO_LICB1R blockade rescues diet-induced aberrant hippocampal activity/plasticity after training C_LIO_LIObesogenic diet enhances hippocampal endocannabinoid levels and CB1R after training C_LIO_LIDeletion of hippocampal CB1R rescues diet-induced long-term memory deficits C_LIO_LIObesogenic diet enhances hippocampal mTOR phosphorylation after training C_LIO_LImTOR inhibition rescues diet-induced memory consolidation deficits C_LI

neuroscience↗

bioRxiv2022

Obesogenic diet induces circuit-specific memory deficits in mice

Obesity is associated with neurocognitive dysfunction, including memory deficits. This is particularly worrisome during adolescence, which represents a crucial period for maturation of brain structures, such as the hippocampus which are crucial for cognition. In rodent models, we recently reported that memory impairments induced by obesogenic high-fat diet (HFD) intake during the periadolescent period can be reversed by chemogenetic manipulation of the ventral hippocampus (vHPC). Here, we used an intersectional viral approach in HFD-fed male mice to chemogenetically inactivate specific vHPC efferent pathways to nucleus accumbens or medial prefrontal cortex during memory tasks. We first demonstrated that HFD enhanced activation of both pathways after training and that our chemogenetic approach was effective in normalising this activation. Inactivation of the vHPC-nucleus accumbens pathway rescued HFD-induced deficits in recognition but not location memory. Conversely, inactivation of the vHPC-medial prefrontal cortex pathway restored location but not recognition memory impairments produced by HFD. Either pathway manipulation did not affect exploration, locomotion or anxiety-like behaviour. These findings suggest that HFD intake throughout adolescence impairs different types of memory through overactivation of specific hippocampal efferent pathways and that targeting these overactive pathways has therapeutic potential.

neuroscience↗

bioRxiv2020

Chemogenetic silencing of hippocampus and amygdala reveals a double dissociation in periadolescent obesogenic diet-induced memory alterations

1In addition to numerous metabolic comorbidities, obesity is associated with several adverse neurobiological outcomes, especially learning and memory alterations. Obesity prevalence is rising dramatically in youth and is persisting in adulthood. This is especially worrying since adolescence is a crucial period for the maturation of certain brain regions playing a central role in memory processes such as the hippocampus and the amygdala. We previously showed that periadolescent exposure to obesogenic high-fat diet (HFD) had opposite effects on hippocampus- and amygdala-dependent memory, impairing the former and enhancing the latter. However, the causal role of these two brain regions in periadolescent HFD-induced memory alterations remains unclear. Here, we first showed that periadolescent HFD induced long-term, but not short-term, object recognition memory deficits, specifically when rats were exposed to a novel context. Using chemogenetic approaches to inhibit targeted brain regions, we then demonstrated that recognition memory deficits are dependent on the activity of the ventral hippocampus, but not the basolateral amygdala. On the contrary, the HFD-induced enhancement of conditioned odor aversion requires specifically amygdala activity. Taken together, these findings suggest that HFD consumption throughout adolescence impairs long-term object recognition memory through the overactivation of the ventral hippocampus during memory acquisition. Moreover, these results further highlight the bidirectional effects of adolescent HFD on hippocampal and amygdala functions.

neuroscience↗