Ricerc@Sapienza

Hippocampal organotypic cultures constitute a very easy but delicate method widely used to study amyloid β-peptide toxicity. This ex vivo technique is performed on tissues isolated from newborn rats. Here, we describe a protocol for the preparation and culture of hippocampal organotypic slices that can be maintained for 14-21 days and their application to the study of amyloid β-peptide toxicity.

Brain systems underlying human memory function have been classically investigated studying patients with selective memory impairments. The discovery of rare individuals who have highly superior autobiographical memory (HSAM) provides, instead, an opportunity to investigate the brain systems underlying enhanced memory. Here, we carried out an fMRI investigation of a group of subjects identified as having HSAM. During fMRI scanning, eight subjects with HSAM and 21 control subjects were asked to retrieve autobiographical memories (AMs) as well as non-AMs (e.g., examples of animals).

Chronic stress induces maladaptive neural responses in several brain areas including hippocampus. It has been demonstrated that chronic stress exposure induced a downregulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors, which would reduce the negative feedback role exerted by these receptors. The reduced availability of these receptors would enhance glutamate overflow in the hippocampus, supporting the hypothesis that hippocampal glutamatergic neurotransmission plays a key etiopathological determinant in stress-induced neuropsychiatric disorders.

Microglia are the resident immune cells of the central nervous system (CNS). In the last year, the improvements in the transgenic mouse technologies and imaging techniques have shed light on microglia functions under physiological conditions. Microglia continuously scan the brain parenchyma with their highly motile processes, maintaining tissue homeostasis and participating in neuronal circuits refinement.

Deficient neuron-microglia signaling during brain development is associated with abnormal synaptic maturation. However, the precise impact of deficient microglia function on synaptic maturation and the mechanisms involved remain poorly defined. Here we report that mice defective in neuron-to-microglia signaling via the fractalkine receptor (Cx3cr1 KO) show reduced microglial branching and altered motility and develop widespread deficits in glutamatergic neurotransmission.

Exposure of the mother to adverse events during pregnancy is known to induce pathological programming of the HPA axis in the progeny, thereby increasing the vulnerability to neurobehavioral disorders. Maternal care plays a crucial role in the programming of the offspring, and oxytocin plays a key role in mother/pup interaction.

An increasing number of studies show that selective serotonin reuptake inhibitors (SSRIs) exert their therapeutic action, at least in part, by amplifying the influence of the living environment on mood. As a consequence, when administered in a favorable environment, SSRIs lead to a reduction of symptoms, but in stressful conditions, they show limited efficacy. Therefore, novel therapeutic approaches able to neutralize the influence of the stressful environment on treatment are needed.

Introduction: Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers. Methods: Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose–positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117).

The gliotransmitter glutamate in different brain regions modulates neuronal excitability and synaptic transmission through a variety of mechanisms. Among the hallmarks of astrocytic glutamate release are the slow depolarizing inward currents (SICs) in neurons mediated by N-methyl-d-aspartate receptor activation. Different stimuli that evoke Ca 2+ elevations in astrocytes induce neuronal SICs suggesting a Ca 2+ -dependent exocytotic glutamate release mechanism of SIC generation.

Aims. Prion protein (PrPC), like many GPI-anchored protein, is found in sphingolipid-rich membrane microdomains known as lipid raft. This membrane-bound isoform dimerizes and can act as cell surface receptor, co-receptor or form multimolecular complexes and recruit downstream signal transduction pathways. As known, dimerization of membrane-bound PrPC leads to clustering in multimolecular complexes and serves to regulate different aspect of neuronal homeostasis, while intracellular dimerization appears to be the most relevant event in neuroprotection, via N1 and C1 prion metabolites.