Bax deletion does not protect neurons from BSE-induced death

Area of Science:

• Neuroscience
• Molecular Biology
• Pathology

Background:

• Neurodegeneration is a hallmark of prion diseases, but the exact mechanisms of neuronal death remain unclear.
• The BAX protein, crucial for mitochondrial apoptosis, has been linked to neuronal death in inherited prion diseases.
• It is unknown if similar mechanisms drive neurodegeneration in infectious prion diseases.

Purpose of the Study:

• To investigate the role of the BAX protein in neuronal death caused by an infectious prion disease.
• To determine if BAX is necessary for neurodegeneration in a mouse model of bovine spongiform encephalopathy (BSE).

Main Methods:

• Inoculation of a mouse-adapted BSE strain into mice lacking the Bax gene (Bax-/-) and wild-type littermates.
• Assessment of disease progression, clinical signs, PrP(res) deposition, astrogliosis, and neuronal integrity.

Main Results:

• Bax gene inactivation did not prevent disease development or clinical illness.
• Prion protein (PrP(res)) deposition and astrogliosis proceeded normally in Bax-/- mice.
• Neuronal integrity was not preserved, and neurons in the hippocampus and thalamus were not protected.

Conclusions:

• The BAX protein is not required for neuron death induced by the BSE prion strain.
• These findings indicate that BAX-independent molecular pathways are involved in neurodegeneration during infectious prion diseases.
• Multiple cell death mechanisms likely contribute to the pathology of prion diseases.