CELLULAR AND MOLECULAR CHANGES IN THE SPINAL CORD THAT CAUSE MOTOR DEFICITS IN OLD AGE - THE CAPACITY TO CA…

Assistance award details

Assistance award identifier

ASST_NON_K00AG068442_075

FAIN

K00AG068442

Recipient

THE GENERAL HOSPITAL CORPORATION

Awarding agency

Department of Health and Human Services

Funding agency

Department of Health and Human Services

Assistance listing (CFDA)

93.866

Total obligated

$243,934

Period

Sep 30, 2020 – Jan 31, 2026

Fiscal year

2023

Place of performance state

MA

Source file

FY2023_All_Assistance_Full_20261006.zip

Description

CELLULAR AND MOLECULAR CHANGES IN THE SPINAL CORD THAT CAUSE MOTOR DEFICITS IN OLD AGE - THE CAPACITY TO CARRY OUT SOMATIC MOTOR FUNCTIONS PROGRESSIVELY DIMINISHES WITH ADVANCING AGE, HAVING A SIGNIFICANT EFFECT ON THE OVERALL HEALTH OF INDIVIDUALS. THEREFORE, IT IS IMPERATIVE TO ELUCIDATE THE CELLULAR AND MOLECULAR MECHANISMS UNDERLYING AGE-DEPENDENT MOTOR DEFICITS, AS THIS INFORMATION IS NECESSARY TO DEVELOP TREATMENTS THAT PRESERVE AND RESTORE MOTOR FUNCTION IN OLD AGE. A-MOTOR NEURONS ARE THE EFFECTOR CELLS OF THE MOTOR SYSTEM AND ARE ESSENTIAL TO ALL VOLUNTARY MOVEMENT. THE COMPLEX CIRCUITS CREATED BY THEIR SYNAPSES IN THE SPINAL CORD INTEGRATE MOTOR COMMANDS AND SENSORY FEEDBACK, AND THEREBY MAKE VITAL CONTRIBUTIONS TO THE PROPER EXECUTION OF COMPLEX MOVEMENTS SUCH AS MAINTAINING BALANCE, COORDINATION, AND FINE MOTOR CONTROL. UNFORTUNATELY, THE ABILITY TO PERFORM THESE MOTOR FUNCTIONS DIMINISHES WITH ADVANCING AGE IN HUMANS, SUGGESTING THAT THE UNDERLYING SYSTEM UNDERGOES DELETERIOUS CHANGES. IN THIS REGARD, THE CANDIDATE RECENTLY DISCOVERED THAT THE NUMBER OF GLUTAMATERGIC, CHOLINERGIC, AND GABAERGIC SYNAPTIC INPUTS ONTO THE SOMATA OF A-MOTOR NEURONS IS SIGNIFICANTLY DECREASED IN AGED MICE. MEANWHILE, GLYCINERGIC INPUTS APPEAR TO BE UNCHANGED, AS DO THE NUMBER AND SIZE OF A-MOTOR NEURON SOMATA. THESE FINDINGS SUGGEST SIGNIFICANT CHANGES TO THE FUNCTIONAL CAPACITY OF THE MOTOR NEUROCIRCUITRY AND REQUIRE THAT THE FULL EXTENT OF THESE SYNAPTIC ALTERATIONS BE ELUCIDATED. FURTHER, IT MUST BE DETERMINED WHETHER A-MOTOR NEURONS AND SPINAL CORD-RESIDENT GLIA UNDERGO INTRINSIC CHANGES THAT MITIGATE OR EXACERBATE THESE ALTERATIONS DURING AGING. THESE GAPS IN KNOWLEDGE HAVE LED TO THE FOLLOWING RESEARCH QUESTIONS: 1) DO THE DENDRITIC ARBORS OF A-MOTOR NEURONS AND THE SYNAPSES THEY CREATE DEGENERATE WITH ADVANCING AGE? 2) DO A-MOTOR NEURONS UNDERGO INTRINSIC AGE-RELATED CHANGES TO THEIR BIOPHYSICAL PROPERTIES? 3) WHAT ROLE DO GLIAL CELLS, SUCH AS MICROGLIA AND ASTROCYTES