Université de Fribourg

Smell, an underrated early biomarker for brain aging

Brai, Emanuele ; Hummel, Thomas ; Alberi, Lavinia

In: Frontiers in Neuroscience, 2020, vol. 14, p. -

Olfaction is in addition to touch the most ancient of our senses, developing already in the womb it decays progressively from 65 years of age with a more pronounced impairment associated with dementia. Despite its clinical relevance and testing accessibility, smell remains an overlooked biomarker, which is rarely used by neurologists in the early screening phase. In this perspective article,...

Université de Fribourg

Olfactory dysfunction in the pathophysiological continuum of dementia

Bathini, Praveen ; Brai, Emanuele ; Alberi Auber, Lavinia

In: Ageing Research Reviews, 2019, vol. 55, p. 100956

Sensory capacities like smell, taste, hearing, vision decline with aging, but increasing evidence show that sensory dysfunctions are one of the early signs diagnosing the conversion from physiological to pathological brain state. Smell loss represents the best characterized sense in clinical practice and is considered as one of the first preclinical signs of Alzheimer’s and Parkinson’s...

Université de Fribourg

Progressive signaling changes in the olfactory nerve of patients with Alzheimer’s disease

Bathini, Praveen ; Mottas, Antoine ; Jaquet, Muriel ; Brai, Emanuele ; Alberi, Lavinia

In: Neurobiology of Aging, 2019, vol. 76, p. 80–95

Olfaction declines with aging and appears to be a prodromal sign of cognitive decline in progressive neurodegenerative diseases. Nevertheless, very little is known about the pathophysiological changes underlying smell loss that may reflect early network dysfunction. A cross-sectional histoanatomical study was conducted on postmortem olfactory nerves of patients with increasing severity of...

Université de Fribourg

Notch1 hallmarks fibrillary depositions in sporadic Alzheimer’s disease

Brai, Emanuele ; Raio, Noemi Alina ; Alberi, Lavinia

In: Acta Neuropathologica Communications, 2016, vol. 4, p. 64

Background: Notch1 signaling is a cellular cascade with a fundamental role from brain development to adult brain function. Reduction in Notch1 affects synaptic plasticity, memory and olfaction. On the other hand, Notch1 overactivation after brain injury is detrimental for neuronal survival. Some familial Alzheimer’s disease (FAD) mutations in Presenilins can affect Notch1...

Université de Fribourg

Notch1 regulates hippocampal plasticity through interaction with the reelin pathway, glutamatergic transmission and CREB signaling

Brai, Emanuele ; Marathe, Swananda ; Astori, Simone ; Fredj, Naila Ben ; Perry, Elisabeth ; Lamy, Christophe ; Scotti, Alessandra ; Alberi, Lavinia

In: Frontiers in Cellular Neuroscience, 2015, p. 447

Notch signaling plays a crucial role in adult brain function such as synaptic plasticity, memory and olfaction. Several reports suggest an involvement of this pathway in neurodegenerative dementia. Yet, to date, the mechanism underlying Notch activity in mature neurons remains unresolved. In this work, we investigate how Notch regulates synaptic potentiation and contributes to the establishment...

Université de Fribourg

Notch signaling in response to excitotoxicity induces neurodegeneration via erroneous cell cycle reentry

Marathe, Swananda ; Liu, S. ; Brai, Emanuele ; Kaczarowski, M. ; Albéri, Lavinia

In: Cell Death & Differentiation, 2015, p. -

Neurological disorders such as Alzheimer’s disease, stroke and epilepsy are currently marred by the lack of effective treatments to prevent neuronal death. Erroneous cell cycle reentry (CCR) is hypothesized to have a causative role in neurodegeneration. We show that forcing S-phase reentry in cultured hippocampal neurons is sufficient to induce neurodegeneration. We found that kainic-acid...

Université de Fribourg

Notch1 activity in the olfactory bulb is odour-dependent and contributes to olfactory behaviour

Brai, Emanuele ; Marathe, Swananda ; Zentilin, Lorena ; Giacca, Mauro ; Nimpf, Johannes ; Kretz, Robert ; Scotti, Alessandra ; Alberi, Lavinia

In: European Journal of Neuroscience, 2014, vol. 40, no. 10, p. 3436–3449

Notch signalling plays an important role in synaptic plasticity, learning and memory functions in both Drosophila and rodents. In this paper, we report that this feature is not restricted to hippocampal networks but also involves the olfactory bulb (OB). Odour discrimination and olfactory learning in rodents are essential for survival. Notch1 expression is enriched in mitral cells of the mouse...

Université de Fribourg

The nuclear receptor REV-ERBα regulates Fabp7 and modulates adult hippocampal neurogenesis

Schnell, Anna ; Chappuis, Sylvie ; Schmutz, Isabelle ; Brai, Emanuele ; Ripperger, Jürgen A. ; Schaad, Olivier ; Welzl, Hans ; Descombes, Patrick ; Alberi, Lavinia ; Albrecht, Urs

In: PLoS ONE, 2014, vol. 9, no. 6, p. e99883

The function of the nuclear receptor Rev-erbα (Nr1d1) in the brain is, apart from its role in the circadian clock mechanism, unknown. Therefore, we compared gene expression profiles in the brain between wild-type and Rev-erbα knock-out (KO) animals. We identified fatty acid binding protein 7 (Fabp7, Blbp) as a direct target of repression by REV-ERBα. Loss of Rev-erbα manifested in memory and...

Université de Fribourg

Notch signaling in the brain: In good and bad times

Alberi, Lavinia ; Hoey, Sarah ; Brai, Emanuele ; Scotti, Alessandra ; Marathe, Swananda

In: Ageing Research Reviews, 2013, p. -

Notch signaling is an evolutionarily conserved pathway, which is fundamental for neuronal development and specification. In the last decade, increasing evidence has pointed out an important role of this pathway beyond embryonic development, indicating that Notch also displays a critical function in the mature brain of vertebrates and invertebrates. This pathway appears to be involved in neural...