Taurine Deficiency and MELAS Are Closely Related Syndromes - Advances in Experimental Medicine and Biology - page 148

patients exhibited exercise intolerance (Sproule et al. 2007 ) . Not surprisingly, many
MELAS patients show an unusual increase in lactic acid production upon exercise,
an effect consistent with reduced respiratory chain activity (Hilton 1995 ) .
Taurine treatment enhances physical endurance (Yatabe et al. 2003 ) while tau-
rine deficiency leads to exercise intolerance (Ito et al. 2008 ; Warskulat et al. 2004 ) .
The symptom of muscle weakness in taurine transporter knockout mice has been
attributed to the loss of muscle mass, diminished muscle size, and an increase in
intracellular lactate content, effects that are comparable to those observed in MELAS
patients.

16.2.7 Neurologic Defects in MELAS and Taurine De fi ciency

MELAS is associated with several neurological and visceral manifestations. The
term “stroke-like episodes” was adopted to distinguish the nonischemic origin of
the MELAS symptom from the ischemic nature of thrombotic strokes. Possible
causes of the “stroke-like episodes” are vascular dysfunction (Silbert et al. 1996 )
and neuronal hyperexcitability that progresses to epileptic activity in the surround-
ing cortex, which in turn mediates capillary damage and triggers the spread of
cerebral lesions (Iizuka and Sakai 2005 ). Inability of cortical cells to cope with
mitochondrial dysfunction also leads to neurological deficits, which are made
worse by mitochondria-mediated oxidative stress and angiopathy (Sue et al. 1998 ) .
As the neuropathy progresses, cortical atrophy, linked to extensive neuronal loss,
is observed (Turnbull et al. 2010 ). Ultimately, an increase in the frequency of sei-
zures can culminate in fatal status epilepticus (Chiang et al. 1995 ) .
Taurine-deficient animals are also susceptible to the development of seizures
(Pasantes-Morales et al. 1987 ; Trachtman et al. 1988 ) , a phenomenon initially
attributed to the “inhibitory neurotransmitter” activity of taurine (Trachtman et al.
1988 ). Taurine deficiency also alters the density of GABA A and the glutamatergic
system in specific brain regions, leading to changes in synaptic activity (Oermann
et al. 2005 ; Sergeeva et al. 2007 ). The encephalopathy that develops in taurine
deficiency exhibits changes in the GABA A system similar to those described for
hepatic encephalopathy (Sergeeva et al. 2007 ). However, the possibility that abnor-
malities of the taurine-deficient brain might arise from the deficiency of energy
supply and oxidative stress has not been considered. Also unclear is the role of tau-
rine deficiency in the progression of cerebral cortex atrophy (Harris et al. 1997 ) .

16.2.8 Opthalmic Defects of MELAS and Taurine De fi ciency

The prevalence of opthalmic abnormalities in MELAS is modest, with the incidence
in one study ranging from 20% for optic atrophy to 16% for pigmentary retinopathy
(Thambisetty et al. 2002 ). Interestingly, abnormalities in retinal pigmentation vary