Elevation in Late-Life Depression of Intercellular Adhesion Molecule-1 Expression in the Dorsolateral Prefrontal Cortex

Abstract

These findings support the vascular depression hypothesis, which has important implications for the understanding and management of late-life depression.

Simultaneous measurement of 23 plasma cytokines in late-life depression

“…This hypothesis is based on the vascular depression model of late-life depression, which is supported by reports on increases in the levels of both ICAM-1 and VCAM-1 in the cerebrovascular endothelium [13,14] and other reports on increases in the levels of proinflammatory cytokines in late-life depression [15]. Table 2 Comparison of 23 plasma cytokine levels using bioplex assays Plasma cytokine levels (pg/ml) Normal control (n = 38) Late-life depression (n = 18) T P IL-2ra interleukin-2 receptor alpha, CTACK cutaneous T-cell-attracting chemokine, GRO-a growth-regulated protein-alpha, HGF hepatocyte growth factor, ICAM-1 intercellular adhesion molecule-1, IFN-a2 interferon-alpha2, LIF leukemia inhibitory factor, MCP-3 monocyte chemotactic protein 3, M-CSF macrophage colony-stimulating factor, MIF migration inhibitory factor, MIG monokine induced by gamma interferon, b-NGF beta-nerve growth factor, SCF stem cell factor, SCGF-b stem cell growth factor-beta, SDF-1a stromal cell-derived factor-1alpha, TNF-b tumor necrosis factor-beta, TRAIL TNF-related apoptosis-inducing ligand, VCAM-1 vascular cell adhesion molecule-1…”

“…Late-life depression has been associated with vascular diseases and with increases in the levels of circulating cytokines and cell-adhesion molecules (CAMs) in the prefrontal cortex [13]. This hypothesis is based on the vascular depression model of late-life depression, which is supported by reports on increases in the levels of both ICAM-1 and VCAM-1 in the cerebrovascular endothelium [13,14] and other reports on increases in the levels of proinflammatory cytokines in late-life depression [15].…”

The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression

“…Moreover, increased expression of ICAM-1 was found in the prefrontal cortex of elder depressive patients. 121 ICAM-1 is a type 1 related protein and a cell adhesion molecule expressed on macrophages and lymphocytes. Increased expression of ICAM-1 is observed in inflammatory processes, it promotes the influx of peripheral immune cells through the BBB.…”

Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

“…The potential functional significance of these effects is supported by the demonstration that overexpression of the glucose transporter blocks the neurotoxic effects of neuronal insults (Figure 1) (Manji and Duman 2001;Sapolsky 2000). Such processes may conceivably also play a role in the relationship between mood disorders and cerebrovascular events, considering that individuals who develop their first depressive episode in late life have an increased likelihood of showing MRI evidence of cerebrovascular disease (Chemerinski and Robinson 2000;Drevets 2000;Kumar et al 1997;Murray and Lopez 1997;Steffens and Krishnan 1998;Steffens et al 1999); furthermore, inflammatory reactions consistent with ischemia are also suggested by the findings of elevations of the intercellular adhesion molecule-1 in dorsolateral PFC in postmortem studies of late-life depression patients (Thomas et al 2000(Thomas et al , 2002). The precise mechanisms by which glucocorticoids exert these deleterious effects remain to be fully elucidated, but likely involve the inhibition of glucose transport (thereby diminishing capability of energy production and augmenting susceptibility to hypoglycemic conditions), and the aberrant, excessive facilitation of glutamatergic signaling (Sapolsky 2000).…”