Age-dependent decline in density of human nerve and spinal ganglia neurons expressing the α3 isoform of Na/K-ATPase

Abstract

Ambulatory instability and falls are a major source of morbidity in the elderly. Age-related loss of tendon reflexes is a major contributing factor to this morbidity, and deterioration of the afferent limb of the stretch reflex is a potential contributing factor to such age-dependent loss of tendon reflexes. To evaluate this, we assessed the number and distribution of muscle spindle afferent fibers in human sacral spinal ganglia (S1) and tibial nerve samples obtained at autopsy, using immunohistochemical staining for the α3 isoform of Na+,K+-ATPase (α3NKA), a marker of muscle spindle afferents. Across all age groups, an average of 26±4% of myelinated fibers of tibial nerve and 17±2% of ganglion neuronal profiles were α3NKA-positive (n=8 per group). Subject age explained 85% of the variability in these counts. The relative frequency of α3NKA-labeled fibers/neurons starts to decline during the 5th decade of life, approaching half that of young adult values in 65-year-old subjects. At all ages, α3NKA-positive neurons were among the largest of spinal ganglia neurons. However, as compared to younger subjects, the population of α3NKA-positive neurons from advanced-age subjects showed diminished numbers of large (both moderately and strongly labeled), and medium-sized (strongly labeled) profiles. Considering the critical significance of ion transport by NKA for neuronal activity, our data suggest that functional impairment and, also, most likely atrophy and/or degeneration of muscle spindle afferents, are mechanisms underlying loss of tendon reflexes with age. The larger and more strongly α3NKA-expressing spindle afferents appear to be proportionally more vulnerable.

Old adults preserve motor flexibility during rapid reaching

“…Indeed, old compared with young adults have deficits in muscle strength (Faulkner et al 2007 ; Thompson 2009 ), muscle power (Bassey et al 1992 ; Faulkner et al 2007 ; Thompson 2009 ) and mobility (Beijersbergen et al 2013 ), are less able to integrate proprioceptive feedback (Goble et al 2009 ) and to coordinate agonist–antagonist muscle pairs (Hortobágyi and Devita 2006 ), critical in reaching movements. Furthermore, old adults show decrements in central nervous system functioning such as a reduction in motor cortical inhibition (Hortobágyi et al 2006 ; Papegaaij et al 2014 ; Peinemann et al 2001 ), white matter lesions (Ge et al 2002 ; Pantoni 2002 ; Schulz et al 2014 ) and decrements in the number and size of afferent fibers (Romanovsky et al 2015 ). Such neuronal and neuromuscular deficits have been associated with impaired and slow execution of ADLs (Rosano et al 2012 ; Sleimen-Malkoun et al 2013 ; Van Halewyck et al 2015 ), poor balance control (Baloh et al 2003 ; Huxhold et al 2006 ; Papegaaij et al 2014 ) and mobility disability in walking (Beijersbergen et al 2013 ; Rosano et al 2012 ; Sorond et al 2015 ).…”

“…Flexibility is the capacity of the neuromuscular system to make fine adjustments in the coordination of the available degrees of freedom (e.g., joint angles) while ensuring successful completion of the intended motor act (Domkin et al 2005 ; Latash et al 2007 ; Scholz and Schöner 1999 ). However, even healthy old adults exhibit subclinical peripheral and central nervous system dysfunctions such as increased agonist–antagonist muscle co-activation, deterioration in the size and number of muscle fibers, and impaired intracortical inhibition, possibly affecting motor flexibly (Bassey et al 1992 ; Beijersbergen et al 2013 ; Faulkner et al 2007 ; Ge et al 2002 ; Goble et al 2009 ; Hortobágyi and Devita 2006 ; Pantoni 2002 ; Papegaaij et al 2014 ; Peinemann et al 2001 ; Romanovsky et al 2015 ; Schulz et al 2014 ; Thompson 2009 ).…”

Flexibility in joint coordination remains unaffected by force and balance demands in young and old adults during simple sit-to-stand tasks

“…For example, old as compared to young adults have an impaired ability to integrate proprioceptive feedback (Goble et al 2009 ) and to coordinate agonist–antagonist muscle pairs (Hortobágyi and Devita 2006 ). Furthermore the central nervous system suffers from a decline in number and size of afferent fibers (Romanovsky et al 2015 ), less cortical and spinal neurons (Dinse 2006 ; Eisen et al 1996 ; Erim et al 1999 ), a reduction in motor cortical inhibition (Hortobágyi et al 2006 ; Papegaaij et al 2014 ; Peinemann et al 2001 ) and cognitive dysfunctions involved in postural control (Morris et al 2016 ; Seidler et al 2011 ; Woollacott and Shumway-Cook 2002 ). Based on these well-established findings on age differences in neuromuscular functions previous studies assumed that flexibility in joint coordination might also decline with ageing.…”

Clock Scan Protocol for Image Analysis: ImageJ Plugins

“…Clock Scan Protocol: The Clock Scan protocol is a fast and simple tool of image analysis. The advantages of this protocol, compared to existing common approaches of image analysis (such as linear pixel intensity scans or calculation of mean pixel intensity of the ROI), have been described in details in previous publications 1,9 . Briefly, this protocol allows the generation of integral radial pixel-intensity profiles by quantifying the intensity of pixels located at different distances from the ROI center such as the object's border, or a pre-determined location outside the object (background).…”

“…The major limitation for distributing and sharing the original protocol was the platform-dependence of its code which was developed with Visual Basic 6.0 (VB) 1,9 . This problem has been recently addressed by one of the research groups at the Leibniz Institute of Molecular Pharmacology, Germany, by developing a similar Fuji ImageJ Clock Scan plugin 2 .…”