BACKGROUND Different mutations in the alpha 1A-subunit of the brain P/Q-type calcium channel gene (CACNA1A) are responsible for familial hemiplegic migraine (FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). Missense and splice site mutations have been found in FHM and episodic ataxia type 2, respectively, whereas a CAG repeat in the CACNA1A gene was found expanded in pati...

Impedance control enables humans to effectively interact with their environment during postural and movement tasks, adjusting the mechanical behavior of their limbs to account for instability. Previous work has shown that people are able to selectively modulate the end-point stiffness of their arms, adjusting for varying directions of environmental disturbances. Behavioral studies also suggest ...

Episodic ataxia type 2 (EA2) is a hereditary cerebellar ataxia associated with mutations in the P/Q-type voltage-gated calcium (Ca(2+)) channels. Therapeutic approaches for treatment of EA2 are very limited. Presently, the potassium (K(+)) channel blocker 4-aminopyridine (4-AP) constitutes the most promising treatment, although its mechanism of action is not understood. Here we show that, in co...

Brain development and interictal function are unaffected in many paroxysmal neurological channelopathies, possibly explained by homoeostatic plasticity of synaptic transmission. Episodic ataxia type 1 is caused by missense mutations of the potassium channel Kv1.1, which is abundantly expressed in the terminals of cerebellar basket cells. Presynaptic action potentials of small inhibitory termina...

Ataxia-telangiectasia mutated kinase (ATM) is a DNA damage-inducible protein kinase, which phosphorylates plethora of substrates participating in DNA damage response. ATM significance for the cell faith is undeniable, since it regulates DNA repair, cell-cycle progress, and apoptosis. Here we describe its main signalling targets and discuss its importance in DNA repair as well as novel findings ...

Stening, E. 2016. The Influence of APOE ε4 on the Hippocampus and HippocampusDependent Memory. Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Social Sciences 130. 85 pp. Uppsala: Acta Universitatis Upsaliensis. ISBN 978-91-554-9685-2. APOE ε4 is the major genetic risk factor for Alzheimer’s disease, a dementia characterized by memory impairment and hippocampal atro...

Subunits of the voltage-gated potassium channel Kv1.1 containing mutations responsible for episodic ataxia (EA), a human inherited neurological disease, were expressed in Xenopus oocytes. Five EA subunits formed functional homomeric channels with lower current amplitudes and altered gating properties compared with wild type. Two EA mutations located in the first cytoplasmic loop, R239S and F249...

Cerebellar ataxia is a prominent clinical symptom in patients with mitochondrial DNA (mtDNA) disease. This is often progressive with onset in young adulthood. We performed a detailed neuropathologic investigation of the olivary-cerebellum in 14 genetically and clinically well-defined patients with mtDNA disease. Quantitative neuropathologic investigation showed varying levels of loss of Purkinj...

The authors describe a large Iranian family with autosomal dominant cerebellar ataxia, which included 14 patients in four generations. We examined seven patients who had expanded CAG repeats in the CACNA1A gene with repeat instability (24 and 25 repeats). Although all patients showed cerebellar ataxia, each patient exhibited peripheral neuropathy or spasticity indicating intrafamilial phenotypi...