Abnormal accumulation of α-synuclein is associated with several neurodegenerative disorders (synucleinopathies), including sporadic Parkinson's disease (PD). Genetic mutations and multiplication of α-synuclein cause familial forms of PD and polymorphisms in the α-synuclein gene are associated with PD risk. Overexpression of α-synuclein can impair essential functions within the cell such as microtubule-dependent transport, suggesting that compounds that act on the microtubule system may have therapeutic benefit for synucleinopathies. In this study, mice overexpressing human wildtype α-synuclein under the Thy1 promoter (Thy1-aSyn) and littermate wildtype control mice were administered daily the microtubule-interacting peptide NAPVSIPQ (NAP; also known as davunetide or AL-108) intranasally for two months starting at one month of age, in a regimen known to produce effective concentrations of the peptide in mouse brain. Motor performance, coordination, and activity were assessed at the end of treatment. Olfactory function, which is altered in PD, was measured one month later. Mice were sacrificed at 4.5 months of age, and their brains examined for proteinase K-resistant α-synuclein inclusions in the substantia nigra and olfactory bulb. NAP-treated Thy1-aSyn mice showed a 38% decrease in the number of errors per step in the challenging beam traversal test and a reduction in proteinase K-resistant α-synuclein inclusions in the substantia nigra compared to vehicle treated transgenics. The data indicate a significant behavioral benefit and a long lasting improvement of α-synuclein pathology following administration of a short term (2 month) NAP administration in a mouse model of synucleinopathy.

The hippocampus, a brain region vital for memory and learning, is sensitive to the damage caused by ischemic/hypoxic stroke and is one of the main regions affected by Alzheimer's disease. The pathological changes that might occur in the hippocampus and its connections, because of cerebral injury in a distant brain region, such as the striatum, have not been examined. Therefore, in the present study, we evaluated the combined effects of endothelin-1-induced ischemia (ET1) in the striatum and β-amyloid (Aβ) toxicity on hippocampal pathogenesis, dictated by the anatomical and functional intra- and inter-regional hippocampal connections to the striatum. The hippocampal pathogenesis induced by Aβ or ET1 alone was not severe enough to significantly affect the entire circuit of the hippocampal network. However, the combination of the two pathological states (ET1 + Aβ) led to an exacerbated increase in neuroinflammation, deposition of the amyloid precursor protein (APP) fragments with the associated appearance of degenerating cells, and blood-brain-barrier disruption. This was observed mainly in the hippocampal formation (CA2 and CA3 regions), the dentate gyrus as well as distinct regions with synaptic links to the hippocampus such as entorhinal cortex, thalamus, and basal forebrain. In addition, ET1 + Aβ-treated rats also demonstrated protracted loss of AQP4 depolarization, dissolution of β-dystroglycan, and basement membrane laminin with associated IgG and dysferlin leakage. Spatial dynamics of hippocampal injury in ET1 + Aβ rats may provide a valuable model to study new targets for clinical therapeutic applications, specifically when areas remotely connected to hippocampus are damaged.

The neurobiological mechanisms of feeding involve the activity of several brain areas as well as the engagement of endogenous compounds such as ghrelin, melanin-concentrating hormone, orexin, neuropeptide Y, leptin, vasoactive intestinal peptide, cholecystokinin, among others. Furthermore, the family of food-intake modulators has been enlarged due to the inclusion of lipids such as N-arachidonoylethanolamide (anandamide), as well as oleoylethanolamide (OEA). In this regard, the food-intake suppressing properties of OEA have been described since pharmacological administration of this compound induces anorexia. It has been suggested that satiety induced by OEA may be through the activation of peroxisome proliferator-activated receptor-α (PPAR-α), a ligand-activated transcription factor that modulates several pathways of lipid metabolism. The mechanism of action of OEA remains unknown, it has been suggested that the ingestion of dietary fat stimulates epithelial cells of the small intestine and promotes the synthesis and release of OEA. Upon its release, this lipid acts within the gut engaging sensory fibers of the vagus nerve to diminish food-intake. Here, recent advances in our understanding of the neurobiological role of OEA in modulation of feeding will be reviewed. Also, we highlight the emerging molecular mechanism of anorexia induced by OEA.

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Newborn rats maintain mother-litter bonds by using olfactory signals. At birth, units in the olfactory glomeruli (OG) are immature and vulnerable to noxious epigenetic factors like undernutrition. Because little is known about the effects of neonatal undernutrition upon the OG morphological organization, different OG parameters were studied in undernourished Wistar rats at 7, 14 and 21 days of age. The issue was addressed by analyzing the olfactory bulb (OB) cross sectional area, the total number and area of OGs in the OB coronal sections, and the distribution of OG area in dorsal and ventral quadrants. Reductions in the OB and OG cross sectional areas were detected at 7 and 14 days posnatally. OG area comparisons by OB quadrants were reduced along the study in quadrants, with larger effects in medial than in lateral OB quadrants. Current OG cytoarchitectonic modifications may affect the newborn capabilities for odour discrimination by disrupting early mother-litter interactions.