Charakterisierung des Einflusses einer Hochfett Diät auf die Neurodegeneration eines Mausmodells für α-Synukleinopathie

In der vorliegenden Arbeit wurden die Auswirkungen der lebenslangen Fütterung einer Hochfett Diät (HFD) auf die Entwicklung der Synukleinopathie sowie der damit einhergehenden motorischen und kognitiven Beeinträchtigungen in (Thy1)-h[A30P]αSyn transgenen Mäusen untersucht. Synukleinopathien, wie die Parkinson Krankheit (PK), gehören zu den häufigsten neurodegenerativen Erkrankungen unserer Zeit, dennoch ist die Pathogenese der PK bis heute nicht genau bekannt. Die A30P Mutation von α-Synuklein (αSyn) wird jedoch mit familiären Fällen der PK assoziiert. Gleichzeitig steigt die Prävalenz von Typ 2 Diabetes mellitus besonders in den Industrieländern rapide an und wird unter anderem mit verschiedenen neurodegenerativen Erkrankungen in Verbindung gebracht. Im Rahmen dieser Arbeit konnte mit Hilfe der HFD die bekannte Synukleinopathie des Mausmodells sowie der damit einhergehenden verhaltensbiologischen Beeinträchtigungen verfrüht induziert werden, was auf einen Einfluss von Übergewicht und gestörter Glukosetoleranz auf die Entwicklung von Synukleinopathie und Neurodegeneration hinweist

The Therapeutic Potential of Metformin in Neurodegenerative Diseases

The search for treatments for neurodegenerative diseases is a major concern in light of today's aging population and an increasing burden on individuals, families, and society. Although great advances have been made in the last decades to understand the underlying genetic and biological cause of these diseases, only some symptomatic treatments are available. Metformin has long since been used to treat Type 2 Diabetes and has been shown to be beneficial in several other conditions. Metformin is well-tested in vitro and in vivo and an approved compound that targets diverse pathways including mitochondrial energy production and insulin signaling. There is growing evidence for the benefits of metformin to counteract age-related diseases such as cancer, cardiovascular disease, and neurodegenerative diseases. We will discuss evidence showing that certain neurodegenerative diseases and diabetes are explicitly linked and that metformin along with other diabetes drugs can reduce neurological symptoms in some patients and reduce disease phenotypes in animal and cell models. An interesting therapeutic factor might be how metformin is able to balance survival and death signaling in cells through pathways that are commonly associated with neurodegenerative diseases. In healthy neurons, these overarching signals keep energy metabolism, oxidative stress, and proteostasis in check, avoiding the dysfunction and neuronal death that defines neurodegenerative disease. We will discuss the biological mechanisms involved and the relevance of neuronal vulnerability and potential difficulties for future trials and development of therapies

The malleable brain: plasticity of neural circuits and behavior: A review from students to students

One of the most intriguing features of the brain is its ability to be malleable, allowing it to adapt continually to changes in the environment. Specific neuronal activity patterns drive long-lasting increases or decreases in the strength of synaptic connections, referred to as long-term potentiation (LTP) and long-term depression (LTD) respectively. Such phenomena have been described in a variety of model organisms, which are used to study molecular, structural, and functional aspects of synaptic plasticity. This review originated from the first International Society for Neurochemistry (ISN) and Journal of Neurochemistry (JNC) Flagship School held in Alpbach, Austria (Sep 2016), and will use its curriculum and discussions as a framework to review some of the current knowledge in the field of synaptic plasticity. First, we describe the role of plasticity during development and the persistent changes of neural circuitry occurring when sensory input is altered during critical developmental stages. We then outline the signaling cascades resulting in the synthesis of new plasticity-related proteins, which ultimately enable sustained changes in synaptic strength. Going beyond the traditional understanding of synaptic plasticity conceptualized by LTP and LTD, we discuss system-wide modifications and recently unveiled homeostatic mechanisms, such as synaptic scaling. Finally, we describe the neural circuits and synaptic plasticity mechanisms driving associative memory and motor learning. Evidence summarized in this review provides a current view of synaptic plasticity in its various forms, offers new insights into the underlying mechanisms and behavioral relevance, and provides directions for future research in the field of synaptic plasticity.Fil: Schaefer, Natascha. University of Wuerzburg; AlemaniaFil: Rotermund, Carola. University of Tuebingen; AlemaniaFil: Blumrich, Eva Maria. Universitat Bremen; AlemaniaFil: Lourenco, Mychael V.. Universidade Federal do Rio de Janeiro; BrasilFil: Joshi, Pooja. Robert Debre Hospital; FranciaFil: Hegemann, Regina U.. University of Otago; Nueva ZelandaFil: Jamwal, Sumit. ISF College of Pharmacy; IndiaFil: Ali, Nilufar. Augusta University; Estados UnidosFil: García Romero, Ezra Michelet. Universidad Veracruzana; MéxicoFil: Sharma, Sorabh. Birla Institute of Technology and Science; IndiaFil: Ghosh, Shampa. Indian Council of Medical Research; IndiaFil: Sinha, Jitendra K.. Indian Council of Medical Research; IndiaFil: Loke, Hannah. Hudson Institute of Medical Research; AustraliaFil: Jain, Vishal. Defence Institute of Physiology and Allied Sciences; IndiaFil: Lepeta, Katarzyna. Polish Academy of Sciences; ArgentinaFil: Salamian, Ahmad. Polish Academy of Sciences; ArgentinaFil: Sharma, Mahima. Polish Academy of Sciences; ArgentinaFil: Golpich, Mojtaba. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Nawrotek, Katarzyna. University Of Lodz; ArgentinaFil: Paid, Ramesh K.. Indian Institute of Chemical Biology; IndiaFil: Shahidzadeh, Sheila M.. Syracuse University; Estados UnidosFil: Piermartiri, Tetsade. Universidade Federal de Santa Catarina; BrasilFil: Amini, Elham. University Kebangsaan Malaysia Medical Centre; MalasiaFil: Pastor, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Wilson, Yvette. University of Melbourne; AustraliaFil: Adeniyi, Philip A.. Afe Babalola University; NigeriaFil: Datusalia, Ashok K.. National Brain Research Centre; IndiaFil: Vafadari, Benham. Polish Academy of Sciences; ArgentinaFil: Saini, Vedangana. University of Nebraska; Estados UnidosFil: Suárez Pozos, Edna. Instituto Politécnico Nacional; MéxicoFil: Kushwah, Neetu. Defence Institute of Physiology and Allied Sciences; IndiaFil: Fontanet, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Turner, Anthony J.. University of Leeds; Reino Unid