Aβ alters the connectivity of olfactory neurons in the absence of amyloid plaques in vivo

نویسندگان

  • Luxiang Cao
  • Benjamin R. Schrank
  • Steve Rodriguez
  • Eric G. Benz
  • Thomas W. Moulia
  • Gregory T. Rickenbacher
  • Alexis C. Gomez
  • Yona Levites
  • Sarah R. Edwards
  • Todd E. Golde
  • Bradley T. Hyman
  • Gilad Barnea
  • Mark W. Albers
چکیده

The amyloid beta peptide aggregates into amyloid plaques at presymptomatic stages of Alzheimer's disease, but the temporal relationship between plaque formation and neuronal dysfunction is poorly understood. Here we demonstrate that the connectivity of the peripheral olfactory neural circuit is perturbed in mice overexpressing human APPsw (Swedish mutation) before the onset of plaques. Expression of human APPsw exclusively in olfactory sensory neurons also perturbs connectivity with associated reductions in odour-evoked gene expression and olfactory acuity. By contrast, olfactory sensory neuron axons project correctly in mice overexpressing wild-type human amyloid precursor protein throughout the brain and in mice overexpressing M671V human APP, a missense mutation that reduces amyloid beta production, exclusively in olfactory sensory neurons. Furthermore, expression of Aβ40 or Aβ42 solely in the olfactory epithelium disrupts the olfactory sensory neuron axon targeting. Our data indicate that altering the structural connectivity and function of highly plastic neural circuits is one of the pleiotropic actions of soluble human amyloid beta.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Human chorionic gonadotropin attenuates amyloid-β plaques induced by streptozotocin in the rat brain by affecting cytochrome c-ir neuron density

Objective(s): Amyloid β plaques, in Alzheimer’s disease, are deposits in different areas of the brain such as prefrontal cortex, molecular layer of the cerebellum, and the hippocampal formation. Amyloid β aggregates lead to the release of cytochrome c and finally neuronal cell death in brain tissue. hCG has critical roles in brain development, neuron differentiation, and function. Therefore, we...

متن کامل

Screening seven Iranian medicinal plants for protective effects against β-Amyloid-induced cytotoxicity in cultured cerebellar granule neurons

Background and objectives: Alzheimer's disease (AD) as a neurodegenerative disorder is the most common form of dementia in the elderly. According to the amyloid hypothesis, accumulation of amyloid beta (Aβ) plaques, which are mostly constituted of Aβ peptide aggregates, triggers pathological cascades that lead to neuronal cell death. Thus, modulation of Aβ toxicity is the hopef...

متن کامل

Effect of creatine supplementation on cognitive performance and apoptosis in a rat model of amyloid-beta-induced Alzheimer's disease

Objective(s): Neuroprotective effect of creatine (Cr) against β-amyloid (Aβ) is reported in an in vitro study. This study investigated the effect of Cr supplementation on β-amyloid toxicity in vivo. Materials and Methods: Thirty two, male Wistar rats were divided into 4 groups. During ten weeks of study, control group went through no surgical or dietary intervention. At the 4th week of study S...

متن کامل

Dietary supplementation with Salvia officinalis L. and aerobic training attenuates memory deficits via the CREB-BDNF pathway in amyloid beta- injected rats

Background: AD is a neurodegenerative disorder in which there is a gathering of beta-amyloid plaques, primarily in the hippocampus, that lead to neuronal death. Exercise training and botanical medications can play a role in the prevention and treatment of neurodegenerative disorders. Objective: The aim of this study was to determine the effects of aerobic training and Salvia officinalis extract...

متن کامل

Vitamin E therapy prevents the accumulation of congophilic amyloid plaques and neurofibrillary tangles in the hippocampus in a rat model of Alzheimer’s disease

Objective(s): Vitamin E may have beneficial effects on oxidative stress and Aβ-associated reactive oxygen species production in Alzheimer’s disease. But, the exact role of vitamin E as a treatment for Alzheimer’s disease pathogenesis still needs to be studied. Hence, we examined the therapeutic effects of vitamin E on the density of congophilic amyloid plaques and neur...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2012